Skip to main content
NCBI home page
Neurotherapeutics logoLink to Neurotherapeutics
. 2025 Jul 29;22(5):e00712. doi: 10.1016/j.neurot.2025.e00712

From metabolism to mind: The expanding role of the GLP-1 receptor in neurotherapeutics

Akash Roy a, Valina L Dawson a,b,c,d,⁎, Ted M Dawson a,b,c,d,⁎
PMCID: PMC12491786  PMID: 40738791

Abstract

GLP-1 receptor agonists (GLP-1RAs), initially approved for diabetes and obesity, are now under investigation for neuroprotective effects in a range of neurological disorders. These agents, whose receptors are widely expressed in brain regions involved in cognition and metabolism, modulate neurotransmitter release and promote neurogenesis. While preclinical studies consistently demonstrate benefits in models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS), clinical trial outcomes have been variable, largely owing to heterogeneity in study populations and trial design. Newer agents, such as NLY01 and tirzepatide, are under development to enhance central nervous system penetration and efficacy. Although GLP-1RAs are generally safe in metabolic conditions, their use in neurological diseases requires careful monitoring and patient selection. Future directions include developing reliable biomarkers, implementing precision medicine strategies, and exploring the use of combination therapies to maximize therapeutic potential.

Keywords: GLP-1 receptor agonists, Neuroprotection, Synaptic plasticity, Central nervous system, Neurodegenerative diseases

Graphical abstract

Image 1

Open in a new tab

Introduction

GLP-1 receptor agonists (GLP-1RAs) are well-established treatments for type 2 diabetes mellitus (T2DM) and obesity, providing effective glycemic control, weight loss, and cardiovascular benefits [[1], [2], [3]]. GLP-1 was first identified in the 1980s as a gut hormone with potent insulin-stimulating effects. This discovery led to the development of pharmacologically stable GLP-1 receptor agonists for diabetes and obesity in the early 2000s. As clinical experience grew, research revealed that GLP-1 receptors are also widely distributed throughout the brain, and that certain GLP-1RAs can cross the blood-brain barrier [4,5]. The GLP-1 receptor, a class B G protein-coupled receptor, is expressed not only on pancreatic β-cells but also in key brain regions involved in metabolic regulation and cognitive function [6,7]. Because native GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4) and neprilysin, resulting in a short half-life, pharmacologically stable GLP-1RAs have been developed to overcome this limitation [3,4]. Beyond their metabolic actions, GLP-1RAs exert central effects by regulating appetite and supporting cardiovascular health [2,4,7]. Importantly, GLP-1 receptors are also present in brain areas essential for cognition and memory, [4,5,7] suggesting a potential role in neurological function. Recent clinical studies have begun to explore the neuroprotective potential of GLP-1RAs in various neurological disorders, though results have been mixed, likely reflecting differences in study design, patient selection, and dosing regimens. The development of dual and triple agonists, including GLP-1/GIP co-agonists, seeks to further enhance neuroprotection in patients with overlapping metabolic and neurological conditions [8]. As research advances, the therapeutic scope of these agents continues to expand [[8], [9], [10]].

Methods

To provide a comprehensive and focused overview of this rapidly evolving field, we conducted a systematic review of the literature.

We searched PubMed, Web of Science, and Embase from inception through April 2025 using the terms “GLP-1 receptor agonists,” “GLP-1RAs,” “neurodegeneration,” “Alzheimer's,” “Parkinson's,” “multiple sclerosis,” “ALS,” “mechanisms,” “clinical trials,” and “biomarkers.” Studies were included if they were English-language, peer-reviewed, and focused on central nervous system effects; non-neurological studies and non-primary research articles (except background reviews) were excluded. Of 217 articles screened by title and abstract, 89 were selected for full-text review. Ultimately, 70 articles were cited based on relevance, methodological quality, and lack of redundancy, ensuring a robust and focused evidence base for this review.

GLP-1R Distribution in the Nervous System

GLP-1 receptors are widely distributed throughout the central nervous system, paralleling the projections of preproglucagon (PPG) neurons from the nucleus tractus solitarii (NTS) to regions involved in energy homeostasis, autonomic regulation, and stress responses [11,12]. High GLP-1R expression is found in hypothalamic nuclei critical for feeding and energy balance, including the arcuate (ARC), paraventricular (PVN), dorsomedial (DMH), and lateral hypothalamic areas [[13], [14], [15]] (Fig. 1). The brainstem-including the area postrema, NTS, and dorsal motor nucleus of the vagus-also shows significant GLP-1R expression, mediating autonomic and visceral functions [13,14,16]. Expression in cortical regions, the hippocampus, caudate putamen, and globus pallidus suggests additional roles in cognition and behavior [13,15]. In the spinal cord, GLP-1Rs are concentrated in sympathetic preganglionic neurons, where brainstem-derived GLP-1 acting as the primary ligand [12,14,16] (Fig. 1). Further studies are required to elucidate the specific functions of GLP-1R across these diverse brain regions.

Fig. 1.

Fig. 1

Open in a new tab

GLP-1 Receptor Distribution in the Nervous System. Schematic illustration showing GLP-1 receptor expression in the brain and spinal cord. High expression is highlighted in hypothalamic nuclei (ARC, PVN, DMH, LHA) and brainstem regions (NTS, area postrema, dorsal motor nucleus). Moderate levels are shown in cortex, hippocampus, caudate putamen, and globus pallidus; lower levels appear in the spinal cord. Color coding indicates relative receptor density.

Presynaptic Modulation of Neurotransmitter Release

GLP-1R modulates synaptic transmission by regulating presynaptic glutamate and GABA release, thereby influencing neural circuits involved in energy balance, cognition, and emotional regulation. In the paraventricular nucleus (PVN), GLP-1 enhances AMPA receptor-mediated excitatory postsynaptic currents, which increases corticotropin-releasing hormone (CRH) neuron activity and promoting anorexigenic signaling [[17], [18], [19]]. In the hippocampus, GLP-1R activation upregulates the AMPA receptor subunit GluR1 and postsynaptic density protein 95 (PSD-95), supporting long-term potentiation (LTP) and memory formation [17,20] (Fig. 2). Pre-synaptically, GLP-1R effects involve PI3K/Akt-dependent vesicle priming whereas postsynaptic actions are mediated by cAMP/PKA-driven AMPA receptor phosphorylation (Fig. 2). In reward-related regions such as the ventral tegmental area (VTA), GLP-1 suppresses GABAergic inhibition, facilitating dopamine signaling and reducing food-motivated behaviors [19,21,22]. GLP-1R activation also promotes hippocampal neurogenesis, enhances spatial memory, and modulates dopaminergic and serotonergic pathways involved in mood and reward [10,[23], [24], [25], [26], [27]]. In neurodegenerative states, these mechanisms converge to restore synaptic plasticity via BDNF/TrkB signaling (Fig. 2). While robust synaptic effects have been demonstrated in animal models, consistent replication in humans remains limited, underscoring the need for translational research and validated biomarkers.

Fig. 2.

Fig. 2

Open in a new tab

Mechanisms of Neurotransmitter Modulation by GLP-1R. (A) Pre and post synaptic modulation of glutamate/GABA release in PVN and VTA via GLP-1R activation (B) Postsynaptic AMPA receptor trafficking via PI3K/Akt pathway, promotes LTP, and supports dopamine signaling. (C) Synaptic restoration pathways (cAMP/PKA, BDNF) in neurodegeneration.

GLP-1R Agonists in Neurodegenerative Diseases

  • A.

    Alzheimer's Disease (AD): Preclinical studies indicate that liraglutide and semaglutide reduce amyloid-β plaque accumulation by modulating amyloid precursor protein processing and enhancing microglial-mediated clearance. These agents inhibit tau hyperphosphorylation, stabilize microtubules, and shift glial cells to anti-inflammatory states, helping preserve synapses and support memory [9,24,28]. Early-phase clinical trials suggest GLP-1RAs may slow cognitive decline and preserve brain volume in mild cognitive impairment and early AD. Liraglutide has demonstrated stabilization of cerebral glucose metabolism, and semaglutide is being evaluated in larger trials [26,27,29,30]. Intranasal delivery of GLP-1RAs, such as exenatide, enhances neuroprotection and cognitive outcomes in AD models [8,31,32]. Phase III EVOKE (NCT04777396) and EVOKE+ (NCT04777409) trials are evaluating the effects of oral semaglutide on AD biomarkers and neuroinflammation in early symptomatic AD [29] (Fig. 3).

  • B.

    Parkinson's Disease (PD): GLP-1RAs address central pathological mechanisms in PD, including neuroinflammation, mitochondrial dysfunction, and protein aggregation [27,[33], [34], [35]]. Exenatide and liraglutide promote neuronal survival and attenuate neuroinflammation via PI3K/Akt signaling, inhibiting apoptosis by modulating Bax, caspase-3, and Bcl-2 [9,24]. They also enhance mitochondrial function by upregulating PGC-1α, restoring energy production and reducing cell death [24]. A recent pivotal study demonstrated that lixisenatide prevented disease progression in PD patients over one year, building on earlier clinical successes [36]. Clinical trials have yielded mixed results: several studies, including a phase II trial of NLY01, failed to meet primary endpoints for motor progression, with only modest or nonsignificant effects overall [37,38]. Subgroup analysis suggested some benefit in younger patients, but larger, targeted studies are needed [37,38] (Fig. 3).

  • C.

    Multiple Sclerosis (MS): GLP-1RAs demonstrate potential in MS through anti-inflammatory and neuroprotective mechanisms. In animal models, exenatide and liraglutide delay disease onset, reduce severity, and promote remyelination by shifting microglia and macrophages from pro-inflammatory to anti-inflammatory phenotypes, lowering cytokine levels [[39], [40], [41]]. These agents enhance oligodendrocyte precursor differentiation and accelerate axonal regeneration, likely via PI3K/Akt and cAMP/PKA signaling pathways [39,42]. Clinical data indicate that GLP-1RAs are generally safe and well-tolerated, with minor side effects such as weight loss. However, long-term efficacy and safety remain to be established, especially concerning metabolic disturbances in advanced disease stages. Larger clinical trials are necessary to confirm these benefits [[39], [40], [41], [42]] (Fig. 3).

  • D.

    Amyotrophic Lateral Sclerosis (ALS): Evidence for GLP-1RAs in ALS is limited but suggests potential benefit through enhancement of antioxidant enzymes, which may slow disease progression [43,44]. Preclinical results are inconsistent, likely due to variability in experimental models and dosing regimens [45]. Well-designed clinical trials are needed to clarify the therapeutic potential of GLP-1RAs in ALS [44,45].

  • E.

    Friedreich ataxia: Recent evidence shows that exenatide, a GLP-1 receptor agonist, induces frataxin expression and improves mitochondrial function in models of Friedreich ataxia, suggesting a potential therapeutic avenue for mitochondrial dysfunction in neurodegenerative diseases [46].

Fig. 3.

Fig. 3

Open in a new tab

Neuroprotective Effects of GLP-1RAs in neurodegenerative diseases. In Alzheimer's disease, GLP-1RAs reduce amyloid-β plaques, tau hyperphosphorylation, and neuroinflammation, while restoring synaptic proteins and dendritic spine density. In Parkinson's disease, GLP-1RAs decrease α-synuclein aggregation, enhance mitochondrial function, activate PI3K/Akt signaling, and reduce neuronal apoptosis. In multiple sclerosis and overall neurodegeneration, GLP-1RAs promote remyelination, shift microglia/macrophages to an anti-inflammatory M2 phenotype, enhance oligodendrocyte precursor differentiation, and support axonal regeneration.

Emerging Biomarkers and Mechanisms in neurodegeneration: GLP-1 receptor agonists inhibit microglial activation and neurotoxic astrocyte transformation through cAMP/PKA and PI3K/Akt signaling pathways. By activating GLP-1Rs on glial cells, these agents suppress pro-inflammatory cytokines (IL-1β, TNF-α) and block NF-κB-mediated inflammatory cascades [10,24]. In microglia, this shifts polarization from pro-inflammatory to anti-inflammatory states, reducing phagocytic hyperactivity and cytokine release. For astrocytes, GLP-1R activation prevents conversion to neurotoxic A1 phenotypes by interrupting microglia-derived IL-1α/TNF-α/C1q signaling [24,47,48], thereby promoting amyloid-β clearance in Alzheimer's disease models [48] and pathogenic α-synuclein in PD models [47]. The agonist NLY01 exemplifies this mechanism by crossing the blood-brain barrier to directly target microglial GLP-1Rs, in addition to blocking dopaminergic neuron loss in Parkinson's models through preventing microglia activation and generation of neurotoxic reactive astrocytes [47] and potentially PI3K/AKT-mediated survival pathways [24] (Fig. 3). Concurrently, it modulates calcium signaling in astrocytes, stabilizing their synaptic support functions while inhibiting reactive transformations.

Novel GLP-1R Agonists in Neurotherapeutics

NLY01 is a pegylated, long-acting GLP-1 receptor agonist designed with a unique peptide sequence that facilitates blood-brain barrier penetration and sustained brain exposure. However, its PEGylation limits CNS entry compared to smaller agonists such as exendin-4 (brain/plasma ratio 0.03 vs. 0.15), making biomarker-guided dosing essential in ongoing clinical trials. Unlike other GLP-1R agonists, NLY01 does not desensitize the GLP-1 receptor, allowing for continuous activation. This persistent engagement of GLP-1R on microglia and astrocytes inhibits microglial activation and prevents the transformation of astrocytes into neurotoxic phenotypes, thereby reducing neuroinflammation and preserving neuronal integrity in models of neurodegenerative diseases such as Parkinson's and Alzheimer's [38,47,48]. It binds GLP-1 receptors on microglia, suppressing pro-inflammatory cytokines and preventing astrocyte transformation into neurotoxic phenotypes, which reduces neuroinflammation and preserves neuronal and synaptic integrity [39,40]. In Parkinson's disease models, NLY01 blocks microglial activation, reduces dopaminergic neuron loss, and improves motor function and survival [47]. Clinically, NLY01 has advanced through a phase II trial for Parkinson's and is approved by the FDA for a phase II trial in Alzheimer's disease. In a phase II Parkinson's trial, NLY01 did not significantly slow motor progression, overall underscoring the challenge of translating preclinical success to clinical efficacy. Subgroup analysis suggested benefits for patients under 60 years old, highlighting the importance of precision medicine. Ongoing development will need to focus on optimizing dosing, managing metabolic side effects, and refining outcome measures [37,38]. Long-acting injectable GLP-1 receptor agonists, such as semaglutide, show neuroprotective effects in Alzheimer's and Parkinson's models [49]. While GLP-1RAs are generally thought to have limited BBB penetration, recent studies indicate that many of these agents are cable of CNS penetration of varying degrees [5,50]. Liraglutide reduces hippocampal atrophy [26] and dopaminergic neuron loss [51], though its shorter half-life requires daily injections [36]. Investigational oral agents such as orforglipron and danuglipron show promising efficacy in phase II trials for glycemic control and weight reduction, offering flexible dosing and improved adherence [52]. Nanoparticle-mediated delivery of GLP-1RAs is being explored to enhance CNS bioavailability [53].

Dual and triple agonists, including tirzepatide and HM15211, target multiple metabolic pathways and have shown promising results in preclinical AD and PD models [8,54,55]. Recent evidence on these agonists highlighted their mechanisms in modulating neuroinflammation. In addition to NLY01, other novel GLP-1R agonists and dual GLP1 and GIP (Glucose-dependent Insulinotropic Polypeptide (GIP) dual agonists among other agents are advancing in preclinical and clinical development, offering promising neurotherapeutic strategies (Table 1).

Table 1.

Comparison of emerging GLP-1R-based therapies for neurodegenerative diseases.

Drug Type Delivery Brain Access Main Effect Used For Stage Notes Half-life Frequency of Dosing
NLY01 GLP-1R agonist (long-acting) Injection Crosses BBB Reduces brain inflammation, protects neurons Parkinson's, Alzheimer's, MS Phase II Works best in younger PD patients ∼10–15 days Once weekly
Semaglutide (Ozempic®, Wegovy®) Long-acting GLP-1R Weekly injection Limited brain access Lowers blood glucose and promotes weight loss Diabetes, Obesity Approved Localized accumulation in the hypothalamus ∼7 days Once weekly
Dulaglutide (Trulicity®) Weekly GLP-1R Injection Low Heart & metabolic benefits Diabetes Approved Not useful for brain disease ∼5 days Once weekly
Liraglutide (Victoza®) Daily GLP-1R Injection Moderate Slows brain shrinkage and neuron loss AD, PD (preclinical) Approved (Diabetes) Short-lasting, needs daily use ∼13 ​h Once daily
Oral Semaglutide (Rybelsus®) Oral GLP-1R Pill (daily) Limited brain access Lowers blood glucose and promotes weight loss Diabetes Approved Under investigation in AD (EVOKE/EVOKE+ trials) Must take on empty stomach ∼1 week Once daily
Orforglipron, Danuglipron Oral GLP-1R (new) Pill (flexible) Unknown Helps with weight and sugar control Diabetes, obesity Phase II Easier to take Unknown Flexible
Tirzepatide (Mounjaro®), NN2006-179 Dual/triple agonist (GLP-1/GIP) Injection Moderate (likely) Boosts cell energy, reduces brain inflammation Metabolic ​+ ​brain diseases Preclinical Multi-target approach ∼5 days Once weekly
DA4-JC, DA5-CH (experimental) Dual GLP-1/GIP agonist (peptide, new) Injection High (engineered to cross BBB) Reduces inflammation, amyloid, protects neurons Alzheimer's, Parkinson's (preclinical/animal) Preclinical Superior to single GLP-1 agonists in models; enhanced brain penetration with cell-penetrating sequence Unknown (peptide-specific, likely multi-day) Flexible (tested daily to weekly in models)
Tirzepatide (Mounjaro®) Dual GLP-1/GIP agonist (approved for diabetes) Injection Moderate (likely) Reduces inflammation, improves metabolism, neuroprotection (animal data) Diabetes, under study for neurodegeneration Approved (diabetes), preclinical (neuro) Well-tolerated, multi-target, being studied for brain effects ∼5 days Once weekly
Open in a new tab

Clinical Trials and Therapeutic Potential

In Parkinson's disease, phase II and III trials of GLP-1RAs have shown mixed results. While exenatide improved motor scores over 48 weeks in some studies, other trials, including those for NLY01, did not meet primary endpoints for disease progression. A Phase III trial of Exenatide in PD (NCT4232969) found that Exenatide was without clinical benefit [56]. Lixisenatide showed disease-modifying effects in the LIXIPARK trial by stabilizing motor symptoms in early PD [36]; however, additional studies are required to confirm these findings. Other GLP1 R agonists have been studied in PD and are reviewed elsewhere [35]. Dual GLP-1/GIP agonists are in preclinical evaluation for synergistic neuroprotection; human trials are in planning stages [33,36,40,44,[57], [58], [59]].

The ELAD trial in Alzheimer's disease (NCT01843075) found that liraglutide stabilized cerebral glucose metabolism, though it did not show significant improvements in cognitive outcomes. The phase III EVOKE trial (NCT04777396) and EVOKE+ trial (NCT04777409) are evaluating semaglutide's effects on cognition and disease biomarkers.

GLP 1R agonists reduce the risk of stroke in diabetic and non-diabetic patients [60,61]. Real-world studies have shown the safety and tolerability of GLP-1RAs in MS [41,62].

GLP-1RAs have a well-established safety profile in metabolic diseases but present unique challenges in neurological populations. Gastrointestinal side effects (nausea, vomiting, diarrhea) may worsen frailty in elderly or neurodegenerative patients. While weight loss is beneficial in diabetes, it may be harmful in advanced neurodegeneration or cachexia [1,57,63,64]. Adherence in real-world settings is often limited by side effects, cost, and perceived lack of benefit, complicating translation from trials to clinical practice (Table 2).

Table 2.

GLP-1 receptor agonists in neurotherapeutics: Agents, mechanisms, and clinical evidence.

Disease/Indication GLP-1RA Agents (with stage) Mechanisms of Action Key Preclinical Findings Key Clinical Trial Outcomes & Status Safety/Notes
Alzheimer's Disease Liraglutide (Phase II), Oral Semaglutide (Phase III), Exenatide (preclinical/Phase II), NLY01 (Phase II) ↓ Amyloid-β, ↓ Tau phosphorylation, anti-inflammatory (microglia/astrocyte shift), ↑ synaptic plasticity, ↑ neurogenesis ↓ Plaques, ↓ tau, ↑ cognition, ↑ synaptic markers, anti-inflammatory effects in animal models Liraglutide: Stabilized cerebral glucose metabolism (ELAD); Oral Semaglutide: (EVOKE/EVOKE+: Ongoing) NLY01: planned Phase II Generally well tolerated; GI side effects; weight loss may be concern in frail patients
Parkinson's Disease Exenatide (Phase II/III), Liraglutide (Phase II), NLY01 (Phase II), Semaglutide (preclinical) ↓ Neuroinflammation, ↑ mitochondrial function (↑ PGC-1α), ↓ apoptosis, ↑ DA neuron survival ↑ Motor function, ↓ dopaminergic neuron loss, ↓ α-synuclein, ↓ inflammation Exenatide: Improved motor scores (Phase II), no clinical benefit (Phase III); NLY01: No overall benefit, but positive in younger subgroup; Lixisenatide: stabilized motor symptoms (LIXIPARK); GI side effects, weight loss; careful use in advanced disease
Multiple Sclerosis Exenatide (preclinical), Liraglutide (preclinical/small clinical), NLY01 (Phase II) ↓ Microglial/macrophage activation, ↑ remyelination, ↑ oligodendrocyte differentiation, anti-inflammatory ↓ Disease severity, ↑ remyelination, ↑ axonal regeneration in animal models Liraglutide: neuroprotection in progressive MS (small studies); real-world safety data supportive Well tolerated; weight loss may be adverse in some
ALS Liraglutide (preclinical), Exenatide (preclinical) ↑ Antioxidant enzymes (SOD), ↓ oxidative stress, neuroprotection Mixed results; some slowing of progression in animal models No major clinical trials yet; preclinical evidence inconsistent Safety profile not established for ALS
Novel/Next-Gen Agents NLY01 (long-acting, CNS-penetrant), Semaglutide (oral/injectable), Tirzepatide (dual agonist), Retatrutide (triple agonist), Nanoparticle/intranasal delivery Enhanced CNS penetration, multi-pathway targeting (GLP-1/GIP/Gcg), improved duration, targeted delivery Improved efficacy, CNS bioavailability, and neuroprotection in animal studies NLY01: Phase II (PD, AD, MS); Semaglutide: Phase III (AD); Tirzepatide: preclinical/early clinical; Nanoparticle/intranasal: preclinical Ongoing evaluation of long-term safety, CNS effects, and metabolic side effects
Open in a new tab

GLP-1RA ​= ​GLP-1 receptor agonist; DA ​= ​dopaminergic; SOD ​= ​superoxide dismutase; GI ​= ​gastrointestinal; AD ​= ​Alzheimer's disease; PD = Parkinson's disease; MS ​= ​multiple sclerosis; ALS ​= ​amyotrophic lateral sclerosis; CNS ​= ​central nervous system; GIP ​= ​glucose-dependent insulinotropic polypeptide; Gcg ​= ​glucagon.

Translating GLP-1RA preclinical success to clinical efficacy is complicated by differences in biological signaling, model systems, and safety profiles, as well as inconsistent or negative results in several clinical trials [6]. Recent advances in PET imaging and fluid biomarkers are improving monitoring of GLP-1RA treatment response [65]. Species-specific microbiome differences and toxicity further complicate safety assessment. Individual variability due to genetics, gender, or psychiatric factors affects efficacy and safety, and long-term outcomes remain uncertain because of limited study durations. Bridging these gaps requires advanced human-based models, computational approaches, and adaptive clinical trials with real-time biomarker feedback [66].

Future Directions and Emerging Applications

The future of GLP-1 receptor agonists (GLP-1RAs) in neurology focuses on multi-receptor agonists, innovative delivery systems, and precision medicine approaches. Dual and triple agonists, such as retatrutide, have demonstrated in preclinical models an ability to reduce amyloid-β and tau pathology, decrease neuroinflammation, and promote neurogenesis and synaptic plasticity in Alzheimer's and Parkinson's disease [8]. Novel delivery methods-including intranasal and nanoparticle-based systems-are being developed to improve brain targeting and minimize systemic side effects. For example, intranasal exenatide achieves high hippocampal concentrations and improves cognitive outcomes in preclinical Alzheimer's models [8,31,32].

Precision medicine strategies, such as APOE4 genotyping and PET imaging, are enabling more individualized treatment approaches for neurodegenerative diseases [67,68]. The development of reliable biomarkers is also critical for monitoring therapeutic response and advancing clinical translation. Beyond neurodegeneration, GLP-1RAs are being investigated for broader neurological conditions, including stroke and traumatic brain injury, due to their neuroprotective and anti-inflammatory properties [69,70]. Ongoing large-scale clinical trials aim to confirm the disease-modifying potential of these agents in both neurodegenerative and neuroinflammatory disorders.

Conclusion

GLP-1 receptor agonists, originally developed for metabolic disorders, have emerged as promising therapeutics for a range of neurological diseases. Preclinical and early clinical studies support their neuroprotective, anti-inflammatory, and synaptic benefits in conditions such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, clinical outcomes have been variable, highlighting the need for optimized trial designs, improved biomarkers, and patient stratification.

Advances in dual/triple agonists, novel delivery systems, and precision medicine are expanding the therapeutic landscape. As ongoing research addresses current challenges, GLP-1RAs are poised to play a significant role in the future management of neurodegenerative and neuroinflammatory diseases.

During the preparation of this work the authors used Perplexity Pro in order to optimize clarity, tone, and academic rigor and to polish the paper. After using this service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Financial Disclosure

AR: Postdoctoral Research Fellow, Johns Hopkins University School of Medicine.

VD: Professor, Johns Hopkins University School of Medicine.

TD: Professor, Johns Hopkins University School of Medicine.

Author Contributions

Akash Roy: Study concept and design, interpretation, first draft of the manuscript, critical revision of the manuscript for important intellectual content.aroy35@jhmi.edu.

Valina L. Dawson: Study concept and design, interpretation, critical revision of the manuscript for important intellectual content, study supervision.vdawson@jhmi.edu.

Ted M. Dawson: Study concept and design, interpretation, critical revision of the manuscript for important intellectual content, study supervision.tdawson@jhmi.edu.

Data Statement

NA.

Funding

This work was supported by a grant from the Freedom Together Foundation. T.M.D. is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases.

Declaration of Competing Interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ted M. Dawson reports financial support was provided by Freedom Together Foundation. Ted M. Dawson reports a relationship with D&D Pharmatech that includes: equity or stocks. Valina L. Dawson reports a relationship with D&D Pharmatech that includes: equity or stocks. Ted M. Dawson has patent #27. US,11123109 B2 – Long-Acting GLP-1R Agonist as a Therapy of Neurological and Neurodegenerative Conditions. issued to Neuraly. Valina L. Dawson has patent #27. US,11123109 B2 – Long-Acting GLP-1R Agonist as a Therapy of Neurological and Neurodegenerative Conditions. pending to Neuraly. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Contributor Information

Valina L. Dawson, Email: vdawson@jhmi.edu.

Ted M. Dawson, Email: tdawson@jhmi.edu.

References

  • 1.Collins L., Costello R.A. StatPearls Publishing LLC.; 2025. Glucagon-Like Peptide-1 Receptor Agonists. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: ryan Costello declares no relevant financial relationships with ineligible companies. (StatPearls publishing copyright © 2025). [PubMed] [Google Scholar]
  • 2.Holst J.J. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409–1439. doi: 10.1152/physrev.00034.2006. [DOI] [PubMed] [Google Scholar]
  • 3.Nauck M.A., Meier J.J. Incretin hormones: their role in health and disease. Diabetes Obes Metabol. 2018;20(Suppl 1):5–21. doi: 10.1111/dom.13129. [DOI] [PubMed] [Google Scholar]
  • 4.Baggio L.L., Drucker D.J. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131–2157. doi: 10.1053/j.gastro.2007.03.054. [DOI] [PubMed] [Google Scholar]
  • 5.West J., Li M., Wong S., Le G.H., Teopiz K.M., Valentino K., et al. Are Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists Central Nervous System (CNS) penetrant: a narrative review. Neurol Ther. 2025;14(4):1157–1166. doi: 10.1007/s40120-025-00724-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Drucker D.J. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740–756. doi: 10.1016/j.cmet.2018.03.001. [DOI] [PubMed] [Google Scholar]
  • 7.Campbell J.E., Drucker D.J. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013;17(6):819–837. doi: 10.1016/j.cmet.2013.04.008. [DOI] [PubMed] [Google Scholar]
  • 8.Nowell J., Blunt E., Edison P. Incretin and insulin signaling as novel therapeutic targets for Alzheimer's and Parkinson's disease. Mol Psychiatry. 2023;28(1):217–229. doi: 10.1038/s41380-022-01792-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Mohammed O., Kelemu T. Incretin-based therapies in Alzheimer's and Parkinson's Disease: advancing neuroprotection with dual and triple agonists-a review. Health Sci Rep. 2025;8(7) doi: 10.1002/hsr2.71065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Müller T.D., Finan B., Bloom S.R., D'Alessio D., Drucker D.J., Flatt P.R., et al. Glucagon-like peptide 1 (GLP-1) Mol Metab. 2019;30:72–130. doi: 10.1016/j.molmet.2019.09.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Trapp S., Brierley D.I. Brain GLP-1 and the regulation of food intake: GLP-1 action in the brain and its implications for GLP-1 receptor agonists in obesity treatment. Br J Pharmacol. 2022;179(4):557–570. doi: 10.1111/bph.15638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Llewellyn-Smith I.J., Reimann F., Gribble F.M., Trapp S. Preproglucagon neurons project widely to autonomic control areas in the mouse brain. Neuroscience. 2011;180:111–121. doi: 10.1016/j.neuroscience.2011.02.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Heppner K.M., Kirigiti M., Secher A., Paulsen S.J., Buckingham R., Pyke C., et al. Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and binding in the male nonhuman primate (Macaca mulatta) brain. Endocrinology. 2015;156(1):255–267. doi: 10.1210/en.2014-1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Cork S.C., Richards J.E., Holt M.K., Gribble F.M., Reimann F., Trapp S. Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain. Mol Metab. 2015;4(10):718–731. doi: 10.1016/j.molmet.2015.07.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Merchenthaler I., Lane M., Shughrue P. Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system. J Comp Neurol. 1999;403(2):261–280. doi: 10.1002/(sici)1096-9861(19990111)403:2<261::aid-cne8>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  • 16.Yamamoto H., Lee C.E., Marcus J.N., Williams T.D., Overton J.M., Lopez M.E., et al. Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. J Clin Investig. 2002;110(1):43–52. doi: 10.1172/JCI15595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Liu J., Conde K., Zhang P., Lilascharoen V., Xu Z., Lim B.K., et al. Enhanced AMPA receptor trafficking mediates the anorexigenic effect of endogenous glucagon-like peptide-1 in the paraventricular hypothalamus. Neuron. 2017;96(4):897–909 e5. doi: 10.1016/j.neuron.2017.09.042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Kabahizi A., Wallace B., Lieu L., Chau D., Dong Y., Hwang E.S., et al. Glucagon-like peptide-1 (GLP-1) signalling in the brain: From neural circuits and metabolism to therapeutics. Br J Pharmacol. 2022;179(4):600–624. doi: 10.1111/bph.15682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Diz-Chaves Y., Herrera-Pérez S., González-Matías L.C., Lamas J.A., Mallo F. Glucagon-Like Peptide-1 (GLP-1) in the integration of neural and endocrine responses to stress. Nutrients. 2020;12(11) doi: 10.3390/nu12113304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Royo M., Escolano B.A., Madrigal M.P., Jurado S. AMPA receptor function in hypothalamic synapses. Front Synaptic Neurosci. 2022;14 doi: 10.3389/fnsyn.2022.833449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Chen X.Y., Chen L., Yang W., Xie A.M. GLP-1 suppresses feeding behaviors and modulates neuronal electrophysiological properties in multiple brain regions. Front Mol Neurosci. 2021;14 doi: 10.3389/fnmol.2021.793004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Williams D.L. The diverse effects of brain glucagon-like peptide 1 receptors on ingestive behaviour. Br J Pharmacol. 2022;179(4):571–583. doi: 10.1111/bph.15535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Chohan M.O., Bragina O., Kazim S.F., Statom G., Baazaoui N., Bragin D., et al. Enhancement of neurogenesis and memory by a neurotrophic peptide in mild to moderate traumatic brain injury. Neurosurgery. 2015;76(2):201–214. doi: 10.1227/NEU.0000000000000577. ; discussion 14 -5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Reich N., Hölscher C. The neuroprotective effects of glucagon-like peptide 1 in Alzheimer's and Parkinson's disease: An in-depth review. Front Neurosci. 2022;16 doi: 10.3389/fnins.2022.970925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Hölscher C. The role of GLP-1 in neuronal activity and neurodegeneration. Vitam Horm. 2010;84:331–354. doi: 10.1016/B978-0-12-381517-0.00013-8. [DOI] [PubMed] [Google Scholar]
  • 26.Hansen H.H., Fabricius K., Barkholt P., Niehoff M.L., Morley J.E., Jelsing J., et al. The GLP-1 receptor agonist liraglutide improves memory function and increases hippocampal CA1 neuronal numbers in a senescence-accelerated mouse model of Alzheimer's disease. J Alzheimers Dis. 2015;46(4):877–888. doi: 10.3233/JAD-143090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Hölscher C. Central effects of GLP-1: new opportunities for treatments of neurodegenerative diseases. J Endocrinol. 2014;221(1):T31–41. doi: 10.1530/JOE-13-0221. [DOI] [PubMed] [Google Scholar]
  • 28.Li Y., Duffy K.B., Ottinger M.A., Ray B., Bailey J.A., Holloway H.W., et al. GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease. J Alzheimers Dis. 2010;19(4):1205–1219. doi: 10.3233/JAD-2010-1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Cummings J.L., Atri A., Feldman H.H., Hansson O., Sano M., Knop F.K., et al. evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease. Alzheimers Res Ther. 2025;17(1):14. doi: 10.1186/s13195-024-01666-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Gejl M., Gjedde A., Egefjord L., Møller A., Hansen S.B., Vang K., et al. In Alzheimer's disease, 6-month treatment with GLP-1 analog prevents decline of brain glucose metabolism: randomized, placebo-controlled, double-blind clinical trial. Front Aging Neurosci. 2016;8:108. doi: 10.3389/fnagi.2016.00108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Kamei N., Okada N., Ikeda T., Choi H., Fujiwara Y., Okumura H., et al. Effective nose-to-brain delivery of exendin-4 via coadministration with cell-penetrating peptides for improving progressive cognitive dysfunction. Sci Rep. 2018;8(1) doi: 10.1038/s41598-018-36210-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Kong F., Wu T., Dai J., Zhai Z., Cai J., Zhu Z., et al. Glucagon-like peptide 1 (GLP-1) receptor agonists in experimental Alzheimer's disease models: a systematic review and meta-analysis of preclinical studies. Front Pharmacol. 2023;14 doi: 10.3389/fphar.2023.1205207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Aviles-Olmos I., Dickson J., Kefalopoulou Z., Djamshidian A., Ell P., Soderlund T., et al. Exenatide and the treatment of patients with Parkinson's disease. J Clin Invest. 2013;123(6):2730–2736. doi: 10.1172/JCI68295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Athauda D., Maclagan K., Skene S.S., Bajwa-Joseph M., Letchford D., Chowdhury K., et al. Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390(10103):1664–1675. doi: 10.1016/S0140-6736(17)31585-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Kalinderi K., Papaliagkas V., Fidani L. GLP-1 receptor agonists: a new treatment in Parkinson's disease. Int J Mol Sci. 2024;25(7) doi: 10.3390/ijms25073812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Meissner W.G., Remy P., Giordana C., Maltête D., Derkinderen P., Houéto J.L., et al. Trial of lixisenatide in early Parkinson's disease. N Engl J Med. 2024;390(13):1176–1185. doi: 10.1056/NEJMoa2312323. [DOI] [PubMed] [Google Scholar]
  • 37.Müller T., Möhr J.D. Negative findings from trials with NLY01 or deferiprone for Parkinson's disease. Lancet Neurol. 2024;23(6):558–559. doi: 10.1016/S1474-4422(24)00097-8. [DOI] [PubMed] [Google Scholar]
  • 38.McGarry A., Rosanbalm S., Leinonen M., Olanow C.W., To D., Bell A., et al. Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2024;23(1):37–45. doi: 10.1016/S1474-4422(23)00378-2. [DOI] [PubMed] [Google Scholar]
  • 39.Gharagozloo M., Smith M.D., Sotirchos E.S., Jin J., Meyers K., Taylor M., et al. Therapeutic potential of a novel glucagon-like peptide-1 receptor agonist, NLY01, in experimental autoimmune encephalomyelitis. Neurotherapeutics. 2021;18(3):1834–1848. doi: 10.1007/s13311-021-01088-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Gharagozloo M., Galleguillos D., Jank L., Sotirchos E.S., Smith M.D., Garton T., et al. The effects of NLY01, a novel glucagon-like peptide-1 receptor agonist, on cuprizone-induced demyelination and remyelination: challenges and future perspectives. Neurotherapeutics. 2023;20(4):1229–1240. doi: 10.1007/s13311-023-01390-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Balshi A., Leuenberger G., Dempsey J., Baber U., Sloane J.A. Glucagon-like peptide-1 agonist safety and efficacy in a multiple sclerosis cohort. Mult Scler Relat Disord. 2025;93 doi: 10.1016/j.msard.2024.106229. [DOI] [PubMed] [Google Scholar]
  • 42.Ammar R.A., Mohamed A.F., Kamal M.M., Safar M.M., Abdelkader N.F. Neuroprotective effect of liraglutide in an experimental mouse model of multiple sclerosis: role of AMPK/SIRT1 signaling and NLRP3 inflammasome. Inflammopharmacology. 2022;30(3):919–934. doi: 10.1007/s10787-022-00956-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Li Y., Chigurupati S., Holloway H.W., Mughal M., Tweedie D., Bruestle D.A., et al. Exendin-4 ameliorates motor neuron degeneration in cellular and animal models of amyotrophic lateral sclerosis. PLoS One. 2012;7(2) doi: 10.1371/journal.pone.0032008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Moțățăianu A., Mănescu I.B., Șerban G., Bărcuțean L., Ion V., Bălaşa R., et al. Exploring the role of metabolic hormones in amyotrophic lateral sclerosis. Int J Mol Sci. 2024;25(10):5059. doi: 10.3390/ijms25105059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Keerie A., Brown-Wright H., Kirkland I., Grierson A., Alix J.J.P., Holscher C., et al. The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1(G93A) and TDP-43(Q331K) transgenic mouse models of ALS. Sci Rep. 2021;11(1) doi: 10.1038/s41598-021-96418-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Igoillo-Esteve M., Oliveira A.F., Cosentino C., Fantuzzi F., Demarez C., Toivonen S., et al. Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia. JCI Insight. 2020;5(2) doi: 10.1172/jci.insight.134221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Yun S.P., Kam T.I., Panicker N., Kim S., Oh Y., Park J.S., et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease. Nat Med. 2018;24(7):931–938. doi: 10.1038/s41591-018-0051-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Park J.S., Kam T.I., Lee S., Park H., Oh Y., Kwon S.H., et al. Blocking microglial activation of reactive astrocytes is neuroprotective in models of Alzheimer's disease. Acta Neuropathol Commun. 2021;9(1):78. doi: 10.1186/s40478-021-01180-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Tipa R.O., Balan D.G., Georgescu M.T., Ignat L.A., Vacaroiu I.A., Georgescu D.E., et al. A systematic review of semaglutide's influence on cognitive function in preclinical animal models and cell-line studies. Int J Mol Sci. 2024;25(9) doi: 10.3390/ijms25094972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Rhea E.M., Babin A., Thomas P., Omer M., Weaver R., Hansen K., et al. Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer's and Parkinson's diseases. Tissue Barriers. 2024;12(4) doi: 10.1080/21688370.2023.2292461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Liu W., Jalewa J., Sharma M., Li G., Li L., Holscher C. Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Neuroscience. 2015;303:42–50. doi: 10.1016/j.neuroscience.2015.06.054. [DOI] [PubMed] [Google Scholar]
  • 52.Karakasis P., Patoulias D., Pamporis K., Stachteas P., Bougioukas K.I., Klisic A., et al. Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials. Metabolism. 2023;149 doi: 10.1016/j.metabol.2023.155710. [DOI] [PubMed] [Google Scholar]
  • 53.Li X., Peng X., Zoulikha M., Boafo G.F., Magar K.T., Ju Y., et al. Multifunctional nanoparticle-mediated combining therapy for human diseases. Signal Transduct Target Ther. 2024;9(1):1. doi: 10.1038/s41392-023-01668-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Alshehri G.H., Al-Kuraishy H.M., Waheed H.J., Al-Gareeb A.I., Faheem S.A., Alexiou A., et al. Tirzepatide: a novel therapeutic approach for Alzheimer's disease. Metab Brain Dis. 2025;40(5):221. doi: 10.1007/s11011-025-01649-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Delvadia P., Dhote V., Mandloi A.S., Soni R., Shah J. Dual GLP-1 and GIP agonist tirzepatide exerted neuroprotective action in a Parkinson's disease rat model. ACS Chem Neurosci. 2025;16(5):818–825. doi: 10.1021/acschemneuro.4c00729. [DOI] [PubMed] [Google Scholar]
  • 56.Vijiaratnam N., Girges C., Auld G., McComish R., King A., Skene S.S., et al. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial. Lancet. 2025;405(10479):627–636. doi: 10.1016/S0140-6736(24)02808-3. [DOI] [PubMed] [Google Scholar]
  • 57.Wilding J.P.H., Batterham R.L., Calanna S., Davies M., Van Gaal L.F., Lingvay I., et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989–1002. doi: 10.1056/NEJMoa2032183. [DOI] [PubMed] [Google Scholar]
  • 58.Husain M., Birkenfeld A.L., Donsmark M., Dungan K., Eliaschewitz F.G., Franco D.R., et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381(9):841–851. doi: 10.1056/NEJMoa1901118. [DOI] [PubMed] [Google Scholar]
  • 59.Frías J.P., Davies M.J., Rosenstock J., Pérez Manghi F.C., Fernández Landó L., Bergman B.K., et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503–515. doi: 10.1056/NEJMoa2107519. [DOI] [PubMed] [Google Scholar]
  • 60.Gera A., Latif F., Borra V., Naz S., Mittal V., Ayoobkhan F.S., et al. Efficacy of glucagon-like peptide-1 receptor agonists for prevention of stroke among patients with and without diabetes: a meta-analysis with the SELECT and FLOW trails. Int J Cardiol Heart Vasc. 2025;57 doi: 10.1016/j.ijcha.2025.101638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Mariscal M., Testai F.D. Emerging treatments for obesity: the role of GLP1 receptor agonists on stroke. Curr Neurol Neurosci Rep. 2025;25(1):36. doi: 10.1007/s11910-025-01423-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Sango K., Takaku S., Tsukamoto M., Niimi N., Yako H. Glucagon-like peptide-1 receptor agonists as potential myelination-inducible and anti-demyelinating remedies. Front Cell Dev Biol. 2022;10 doi: 10.3389/fcell.2022.950623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.De Giorgi R., Ghenciulescu A., Dziwisz O., Taquet M., Adler A.I., Koychev I., et al. An analysis on the role of glucagon-like peptide-1 receptor agonists in cognitive and mental health disorders. Nature Mental Health. 2025;3(3):354–373. [Google Scholar]
  • 64.Soldevila B., Puig-Domingo M. [Safety and tolerability of GLP-1 receptor agonists] Med Clin (Barc) 2014;143(Suppl 2):35–40. doi: 10.1016/S0025-7753(14)70107-1. [DOI] [PubMed] [Google Scholar]
  • 65.Xie Y., Wang Y., Pei W., Chen Y. Theranostic in GLP-1R molecular imaging: challenges and emerging opportunities. Front Mol Biosci. 2023;10 doi: 10.3389/fmolb.2023.1210347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Marchenko O., Fedorov V., Lee J.J., Nolan C., Pinheiro J. Adaptive clinical trials: overview of early-phase designs and challenges. Ther Innov Regul Sci. 2014;48(1):20–30. doi: 10.1177/2168479013513889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Ayyubova G. APOE4 is a risk factor and potential therapeutic target for Alzheimer's disease. CNS Neurol Disord Drug Targets. 2024;23(3):342–352. doi: 10.2174/1871527322666230303114425. [DOI] [PubMed] [Google Scholar]
  • 68.Yamazaki Y., Painter M.M., Bu G., Kanekiyo T. Apolipoprotein E as a therapeutic target in Alzheimer's Disease: a review of basic research and clinical evidence. CNS Drugs. 2016;30(9):773–789. doi: 10.1007/s40263-016-0361-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Harej Hrkac A., Pilipovic K., Belancic A., Juretic L., Vitezic D., Mrsic-Pelcic J. The therapeutic potential of glucagon-like peptide 1 receptor agonists in traumatic brain injury. Pharmaceuticals (Basel) 2024;17(10) doi: 10.3390/ph17101313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Verges B., Aboyans V., Angoulvant D., Boutouyrie P., Cariou B., Hyafil F., et al. Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms. Cardiovasc Diabetol. 2022;21(1):242. doi: 10.1186/s12933-022-01686-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Neurotherapeutics are provided here courtesy of Elsevier

RESOURCES