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. 2023 Dec 20;15:1296919. doi: 10.3389/fnagi.2023.1296919

Table 1.

Details of different studies on inducing agent and their molecular marker expression.

S. No. Title Chemical Neurotoxic mechanism in vivo/in vitro Cell line Reference
Aluminium chloride hexahydrate and Maltol toxicity decreased by using Asiatic acid in in vitro model of AD Aluminium chloride hexahydrate and Maltol Down regulates PI3K/AKT/GSK-3β pathway In vitro SH-SY 5Y cells Mashoque et al. (2018)
PM2.5 exposure worsens oligomeric amyloid beta-induced neuronal damage and enhances NLRP3 inflammasome activation in an Alzheimer’s disease in vitro model. PM2.5 IL-1 production and NLRP3 inflammasome activation are both increased. In vitro Primary microglial cells Wang B. R. et al. (2018)
In an in vitro and in vivo model of Alzheimer’s disease hydroxyurea affects membrane fluidity which further affects neuronal membrane aging Hydroxyurea Increase inAβ levels and decrease in AMPK/ACC/CPT1 pathway In Vivo and in vitro Rat primary cortical neurons Yu and Cheng (2021)

  1. Neuroinflammation in rats caused by inducing AlCl3 and checking the effect of fusion of Curcumin and Resveratrol against it.

  2. Caffeic acid’s effect on aluminium chloride-induced dementia in rats.

 AlCl3 High levels of neuro-inflammation as well as increase in COX-2 expression inhibitor
High levels of AChE		 In vitro and In vivo PC-12 cells
Rat brain homogenate		 Mentis et al. (2021) and Sanajou et al. (2023)
5. In SH-SY5Y and C6 cells treated with 27-hydroxycholesterol, NF-B-mediated inflammatory damage is altered differently. 27-Hydroxycholesterol [In SH-SY5Y]
TNF and iNOS secretion increased, while IL10 secretion decreased; TGF, NFB p65 and p50 expression increased, while COX2 expression decreased.
[In C6 cells]
TLR4 and TGF expression increased, while IL1, IL10, TNF, and iNOS secretion decreased.		 In vitro SH-SY5Y and C6 cells Ma et al. (2019)
6.

  1. Rosiglitazone Embedded Nanocarrier System Has Neuroprotective Potential in Streptozotocin-Induced Alzheimer’s Disease Mice.

  2. In diabetics, sarsasapogenin reduces Alzheimer’s-like encephalopathy.

  3. The interaction of hyperphosphorylated tau and pyroptosis in forskolin and streptozotocin-induced Alzheimer’s disease models.

 Streptozotocin TNF- (tumor necrosis factor) and interleukin-6 levels rise (IL-6).
Increase in AKT/GSK-3β cascade
High levels of hyperphosphorylated tau and increased expression of NLRP1 and caspase-1		 In vitro and in vivo SH-SY5Y cells
SH-SY5Y cells
PC12 cells		 Sarathlal et al. (2021), Tripathi et al. (2019), and Hampel et al. (2018)
7. The Dephosphorylation of p70S6 (Thr389) Kinase as a Marker of L-Glutamate-Induced Excitotoxicity Related to Diabetes Disturbances—an Unusual In Vitro Mode L-Glutamate Increased phosphorylation of p70S6K in Thr389 residue In vitro PC12 cells Rorbach-Dolata et al. (2020)
8.

  1. The ameliorative potential of desalted Salicornia europaea L. extract in a multifaceted Alzheimer’s-like scopolamine-induced amnesic mouse model.

  2. Tert-butyl-4-hydroxy-3-((3-(2-methylpiperidin-yl) propylcarbamoyl)phenyl)carbamoylcarbamoylcarbamoylcarbamoylcarbamoylcarbamoylcarbamoylcarbamoylcarb In Astrocytes Stimulated with Amyloid Beta 1–42 and in a Scopolamine Model, carbamate Has Moderate Protective Activity.

  3. Lavender oil protects mice from scopolamine-induced cognitive deficits and PC12 cells from H2O2-induced cytotoxicity.

  4. Pretreatment of Sulforaphane-Enriched Broccoli Sprouts with Pulsed Electric Fields Its antioxidative ability, mediated by Nrf2-HO-1 activation, reduces neuroinflammation and improves scopolamine-induced amnesia in the mouse brain.

  5. Schisandra chinensis and Ribes fasciculatum Work Together to Prevent Neuronal Cell Death and Scopolamine-Induced Cognitive Impairment in Rats.

  6. Myricetin improves scopolamine-induced memory impairment in mice by inhibiting acetylcholinesterase and decreasing brain iron levels.

 Scopolamine TNF-, IL-1, and IL-6 mRNA levels all increased.
Increase in (TNFα), (IL-1β), (IL-6), and the overexpression of (GFAP)
Increase in LDH, ROS and NO levels.
Decrease in MMP levels
Activates NF-κB signaling
Increased expression of Nrf2 and HO-1
Increase in AChE activity and decreasing MDA level		 In vivo and in vitro BV-2 cells
Astrocyte cells
PC12 cells
BV2 cells
PC 12 cells
SH-SY5Y cells		 Karthivashan et al. (2018), Yang et al. (2021), Rai et al. (2021b), Bhatti et al. (2022), Kawahara et al. (2001), and Tuneva et al. (2006)
9. In vitro and in vivo, curcumin and hesperetinreduce D-galactose-induced brain senescence. D-galactose Up-regulate expression of p16 and p21 and lower expression of SOD1, Gpx1, and catalase In vitro SH-SY5Y cells Lee et al. (2020)
In aged rats, hispidulin prevents sevoflurane-induced memory dysfunction. sevoflurane Increase inAβ accumulation and neuroinflammation.
High level of NF-κB		 In vivo and in vitro H4 cells Huang et al. (2018)

  1. In vivo and in vitro, ginsenoside Rd. protects against okadaic acid-induced neurotoxicity.

  2. Using Mesenchymal Stem Cell-Conditioned Medium, Extracellular Vesicle Mitochondrial Transfer Improves Mitochondrial Dysfunction and Suppresses Apoptosis in Okadaic Acid-Treated SH-SY5Y Cells.

 Okadaic acid High level of protein phosphatase 2A.
Increases p181-tau expression		 In vitro and in vivo
In vitro 		Cortical neurons cell
culture
SH-SY5Y Cells		 Li et al. (2011)
Manganese-induced cognitive impairment is caused by dysregulated APP expression and -secretase processing of APP. MnCl2.4H2O APP, −secretase, and soluble APP alpha protein (sAPP) expression were all inhibited. In vivo and in vitro Neuro-2a (N2a) cells Gu et al. (2018)
In vitro, aluminium causes tau aggregation, but not in vivo. Al-maltolate Induces Tau aggregation In vitro Neuronal cell line (N2a) Mizoroki et al. (2007)
Investigating the molecular mechanisms of neurodegenerative diseases: Differential protein expression in hippocampal cells linked to heavy metal (Pb, As, and MeHg) neurotoxicity. Lead chloride, Sodium metaarsenite, Methyl mercury chloride Depletion of ATP production and Alteration of proteins in complex I–V, Increase in ROS levels In vitro HT-22 cells Karri et al. (2018)
Aluminum Modifies Amyloid1–42 Effects on Neuronal Calcium Homeostasis and Mitochondrial Function in a Triple Transgenic Alzheimer’s Disease Mouse Model. Aluminum Promotes Aβ aggregation
High levels of Ca++ ions		 In vitro Cortical neuronal cultures Drago et al. (2008)

  1. Tranylcypromine, an MAO inhibitor, modifies LPS- and A-mediated neuroinflammatory responses in wild-type mice and an Alzheimer’s disease mouse model.

  2. Piperlongumine Suppresses the NF-KappaB Pathway, which improves Lipopolysaccharide-Induced Amyloidogenesis.

  3. Deoxyelephantopin improves memory impairments caused by lipopolysaccharides (LPS) in rats: evidence for anti-neuroinflammatory properties.

  4. Effects of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis, and memory impairment in vitro and in vivo via inhibition of nuclear factor-kappaB.

  5. Astaxanthin Reduces Lipopolysaccharide-Induced Neuroinflammation, Oxidative Stress, and Memory Dysfunction by Inactivating the Signal Transducer and Activator of Transcription 3 Pathway.

 Lipopolysaccharide Increases IL-1β and IL-6 mRNA levels
Activates NF-κB pathway, It increases the level of neuroinflammation markers (COX-2 and iNOS)
High levels of COX-2 and iNOS expression
Increased expressions of cytosolic group IV phospholipase A2, 5-lipoxygenase and toll-like receptor-4 as well as high level of ROS generation
And Neuroinflammation
High levels of TNF-α, IL-1β and IL-6		 In vitro BV2 microglial cells
BV-2, and primary astrocyte cells
BV-2 microglial cells
BV-2 cells
BV-2 microglial cells		 Park et al. (2020), Gong et al. (2011), Andy et al. (2018), Lee et al. (2012), and Han et al. (2019)
Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo Formaldehyde Increase hyperphosphorylation of tau protein in vitro and in vivo neuroblastoma (N2a) Lu et al. (2013)