Table 1.
Interventions indirectly targeting WβC‐signalling activation (WβC‐AC)‐targeted in the central nervous system
| Intervention | Outcome | References |
|---|---|---|
| Modulation of inflammation and oxidative stress | ||
| NO‐NSAID (in vitro/in vivo) | NO‐NSAID counteracts MPTP‐induced decrease in proliferation and neuronal differentiation potential, and age/MPTP‐induced downregulation of the Nr2‐Hmox1 axis in aged SVZ NSCs via increased WβC‐AC | L'Episcopo et al. (2013), L'Episcopo et al. (2012), L'Episcopo et al. (2011a), L'Episcopo et al. (2011c), L'Episcopo et al. (2010b) |
| L‐NAME (in vitro) | Counteraction of decrease in aged SNpc‐DAergic neuroprotection; striatal DAergic re‐innervation; amelioration of motor deficit via WβC‐AC | |
| Apocynin (in vitro) | L‐NIL and apocynin counteract NO and oxidative stress, promote SVZ‐NSC proliferation and neuronal differentiation | |
| Modulation of Nrf2‐Hmox1 axis | ||
| KMS99220 | Novel morpholine derivative activates Nrf2; orally active in MPTP models, ameliorating degeneration and motor deficit; WβC‐AC involvement to be elucidated | Lee et al. (2018) |
| Proinflammatory cytokines/chemokines | ||
| Chemokines (CCL3, CXCL10, CXCL11), in vitro | Chemokine pretreatment of VM astrocytes and aged astrocytes upregulate Wnt1 expression, promoting neurogenesis and DAergic neurogenesis from adult NSCs and inducing neuroprotection against MPTP/MPP+‐induced injury via WβC‐AC | L'Episcopo et al. (2011a), L'Episcopo et al. (2014a), L'Episcopo et al. (2018a) |
| Tetracyclines | ||
| Minocycline, in vivo | Counteracts TNF‐α‐induced decrease in neurogenesis in 6‐OHDA model of PD; WβC‐AC involvement to be elucidated | Worlitzer et al. (2012) |
| Herbal derivatives | ||
| Curcumin (from the rhizome of turmeric), in vivo | Counteracts bisphenol‐induced inhibition of hippocampal neurogenesis via WβC‐AC | Tiwari et al. (2019) |
| Protects against oxidative stress‐induced injury in a rat model of PD via WβC‐AC | Wang, et al. (2017) | |
| Ameliorates cognitive function, enhances neurogenesis, mitigates inflammation and mitochondrial dysfunction in hippocampus in a rodent model of gulf war illeness; WβC‐AC involvement to be elucidated | Kodali et al. (2018) | |
| Exercise, environmental enrichment | Physical activity and environmental enrichment regulate the generation of neural precursors in the adult mouse substantia nigra; WβC‐AC involvement to be elucidated | Klaissle et al. (2012) |
| Endurance exercise promotes neuroprotection against MPTP injury via enhanced neurogenesis, antioxidant capacity and autophagy; WβC‐AC involvement to be elucidated | Jang, kwon, Song, Cosio‐Lima and Lee (2018a), Jang et al. (2018b) | |
| Neural activation | Neural activity‐induced WβC‐AC up‐regulates expression of BDNF. | Zhang, Zhang, Deng, et al., 2018a |
| Neurotrophic factors | BDNF promotes growth of neurons and NSCs, possibly through activation of the PI3K/GSK‐3β/β‐catenin pathway | Li et al. (2017) |
| BDNF promotes human neural stem cell growth via GSK‐3β‐mediated crosstalk with the WβC pathway | Yang et al. (2016) | |
| Optical depolarization | Optogenetic activation of VM astrocytes enhances DAergic differentiation of NSCs and promotes brain repair in PD rodent models; WβC‐AC involvement to be elucidated | Yang et al. (2014) |
| Optical depolarization of DCX‐expressing neuroblasts promotes cognitive recovery and maturation of newborn neurons after traumatic brain injury via WβC‐AC | Zhang, Huang, et al. (2016c) | |
| Coupling of optogenetics and light‐sheet microscopy reveals WβC‐AC during embryogenesis and post‐natal development | Kaur et al. (2017) | |
| WβC‐AC can be controlled in vivo via light responsive capsules. | Ambrosone et al. (2016) | |
| Optical depolarization promoted the maturation of neural stem cells via WβC‐AC | Xia et al. (2014) | |
| Electromagnetic fields | Enhanced olfactory memory in mice exposed to extremely low frequency electromagnetic fields via WβC‐AC‐induced modulation of SVZ‐neurogenesis | Mastrodonato et al. (2018) |
| Transcription factors | ||
| Nurr1 agonists; amodiaquine (AQ), pharmacological stimulation | AQ stimulates Nurr1's transcriptional function, enhancing adult hippocampal neurogenesis; WβC‐AC involvement to be elucidated | Kim et al. (2016) |
| Pharmacological stimulation of Nurr1 induces neuroprotection and anti‐inflammatory effects in the 6‐OHDA PD‐model; WβC‐AC involvement to be elucidated | Smith et al. (2015) | |
| Nanoparticles (Liposomes) | ||
| Curcumin liposomes | Curcumin‐loaded nanoparticles promote adult neurogenesis and reverse cognitive deficits in an Alzheimer's Disease model via WβC‐AC | Tiwari et al. (2017) |
| Paclitaxel liposomes | Collagen microchannel scaffolds carrying paclitaxel‐liposomes induce neuronal differentiation of NSCs through WβC‐AC in spinal cord injury repair | Li et al. (2018) |
6‐OHDA, 6‐hydroxydopamine; BDNF, brain‐derived neurotrophic factor; DA, dopamine; DCX, doublecortin; GSK‐3β, glycogen synthase kinase 3β; Hmox1, heme oxygenase 1; L‐NAME, Nω‐Nitro‐L‐arginine methyl ester hydrochloride; MPP+, 1‐methyl‐4‐phenylpyridinium; MPTP, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine; NO‐NSAID, nitric oxide‐releasing non‐steroidal anti‐inflammatory drugs; Nrf2, nuclear factor erythroid 2‐related factor 2; NSC, neural stem/progenitor cell; Nurr1, nuclear receptor related 1 protein; PI3K, phosphoinositide 3‐kinase; SNpc, substantia nigra pars compacta; SVZ, sub‐ventricular zone; TNF‐α, tumor necrosis factor alpha; VM, ventral midbrain; WβC‐AC, Wnt/β‐catenin signalling activation.
Bold is used to highlight WβC connection