ChAT Cancer Research Results

ChAT, Choline acetyltransferase: Click to Expand ⟱
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Type:
Choline acetyltransferase (ChAT) is the enzyme responsible for synthesizing acetylcholine (ACh), a key neurotransmitter involved in memory, learning, and attention.
In AD, one of the hallmark neurochemical findings is a loss of cholinergic neurons, especially in the basal forebrain, leading to:
↓ ChAT activity
↓ Acetylcholine (ACh) levels
↓ Cognitive function (especially memory and attention)

Many AD drugs aim to increase ACh levels by:
-Inhibiting acetylcholinesterase (AChE) (which breaks down ACh), e.g., donepezil, rivastigmine.


Scientific Papers found: Click to Expand⟱
3271- ALA,    Decrypting the potential role of α-lipoic acid in Alzheimer's disease
- Review, AD, NA
*antiOx↑, Alpha-lipoic acid (α-LA), a natural antioxidant
*memory↑, multiple preclinical studies indicating beneficial effects of α-LA in memory functioning, and pointing to its neuroprotective effects
*neuroP↑, α-LA could be considered neuroprotective
*Inflam↓, α-LA shows antioxidant, antiapoptotic, anti-inflammatory, glioprotective, metal chelating properties in both in vivo and in vitro studies.
*IronCh↑, α-LA leads to a marked downregulation in iron absorption and active iron reserve inside the neuron
*NRF2↑, α-LA induces the activity of the nuclear factor erythroid-2-related factor (Nrf2), a transcription factor.
*BBB↑, capable of penetrating the BBB
*GlucoseCon↑, Fig 2, α-LA mediated regulation of glucose uptake
*Ach↑, α-LA may show its action on the activity of the ChAT enzyme, which is an essential enzyme in acetylcholine metabolism
*ROS↓,
*p‑tau↓, decreased degree of tau phosphorylation following treatment with α-LA
*Aβ↓, α-LA possibly induce the solubilization of Aß plaques in the frontal cortex
*cognitive↑, cognitive reservation of α-LA served AD model was markedly upgraded in additional review
*Hif1a↑, α-LA treatment efficaciously induces the translocation and activity of hypoxia-inducible factor-1α (HIF-1α),
*Ca+2↓, research found that α-LA therapy remarkably declines Ca2+ concentration and calpain signaling
*GLUT3↑, inducing the downstream target genes expression, such as GLUT3, GLUT4, HO-1, and VEGF.
*GLUT4↑,
*HO-1↑,
*VEGF↑,
*PDKs↓, α-LA also ameliorates survival in mutant mice of Huntington's disease [150–151], possibly due to the inhibition of the activity of pyruvate dehydrogenase kinase
*PDH↑, α-LA administration enhances PDH expression in mitochondrial hepatocytes by inhibiting the pyruvate dehydrogenase kinase (PDK),
*VCAM-1↓, α-LA inhibits the expression of cell-cell adhesion molecule-1 and VCAM-1 in spinal cords and TNF-α induced neuronal endothelial cells injury
*GSH↑, α-LA may enhance glutathione production in old-aged models
*NRF2↑, activation of the Nrf2 signaling by α-LA
*hepatoP↑, α-LA also protected the liver against oxidative stress-mediated hepatotoxicity
*ChAT↑, α-LA in mice models may prevent neuronal injury possibly due to an increase in ChAT in the hippocampus of animal models

3438- ALA,    The Potent Antioxidant Alpha Lipoic Acid
- Review, NA, NA - Review, AD, NA
*antiOx↑, Both of alpha lipoic acid and its reduced form have been shown to possess anti-oxidant, cardiovascular, cognitive, anti-ageing, detoxifying, anti-inflammatory, anti-cancer, and neuroprotective pharmacological properties
*cardioP↑,
*cognitive↑, Alpha lipoic acid has the ability to decrease cognitive impairment and may be a successful therapy for Alzheimer’s disease and any disease related dementias
*AntiAge↑,
*Inflam↓,
*AntiCan↑,
*neuroP↑, ALA has neuroprotective effects in experimental brain injury caused by trauma and subarachnoid hemorrhage
*IronCh↑, Also, the ability of ALA to chelate metals can produce an antioxidant effect
*ROS↑, DHLA can exert a pro-oxidant effect of donating its electrons for the reduction of iron, which can then break down peroxide to the prooxidant hydroxyl radical via the Fenton reaction [10]. So, ALA and its reduced form DHLA, can promote antioxidant pr
*Weight↓, α-lipoic acid supplementation at a dose of 300 mg/day might help to could help to promote weight loss and fat mass reduction in healthy overweight/obese women following an energy-restricted balanced diet
*Ach↑, Alpha lipoic acid increases the production of Acetylcholine (Ach) via activating choline acetyl transferase and increases glucose uptake, hence, supplying more acetyl-CoA for the production of Ach of each
*ROS↓, also scavenges reactive oxygen species, thereby increasing the concentration levels of reduced Glutathione (GSH).
*GSH↑,
*lipid-P↓, Alpha lipoic acid can scavenge lipid peroxidation products as hydroxynonenal and acrolein.
*memory↑, learning and memory in the passive avoidance test partially through its antioxidant activity.
*NRF2↑, α-LA treatment has been shown to increase Nrf2 nuclear localization
*ChAT↑, Alpha lipoic acid increases the production of Acetylcholine (Ach) via activating choline acetyl transferase and increases glucose uptake, hence, supplying more acetyl-CoA for the production of Ach of each
*GlucoseCon↑,
*Acetyl-CoA↑,

3550- ALA,    Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer's Disease?
- Review, AD, NA
*antiOx↑, antioxidant and anti-inflammatory properties
*Inflam↓,
*PGE2↓, α-LA has mechanisms of epigenetic regulation in genes related to the expression of various inflammatory mediators, such PGE2, COX-2, iNOS, TNF-α, IL-1β, and IL-6
*COX2↓,
*iNOS↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*BioAv↓, α-LA has rapid uptake and low bioavailability and the metabolism is primarily hepatic
*Ach↑, α-LA increases the production of acetylcholine [30], inhibits the production of free radicals [31], and promotes the downregulation of inflammatory processes
*ROS↓,
*cognitive↑, Studies have shown that patients with mild AD who were treated with α-LA showed a slower progression of cognitive impairment
*neuroP↑, α-LA is classified as an ideal neuroprotective antioxidant because of its ability to cross the blood-brain barrier and its uniform uptake profile throughout the central and peripheral nervous systems
*BBB↑,
*Half-Life↓, α-LA presented a mean time to reach the maximum plasma concentration (tmax) of 15 minutes and a mean plasma half-life (t1/2) of 14 minutes
*BioAv↑, LA consumption is recommended 30 minutes before or 2 hours after food intake
*Casp3↓, α-LA had an effect on caspases-3 and -9, reducing the activity of these apoptosis-promoting molecules to basal levels
*Casp9↓,
*ChAT↑, α-LA increased the expression of M2 muscarinic receptors in the hippocampus and M1 and M2 in the amygdala, in addition to ChaT expression in both regions.
*cognitive↑, α-LA acts on these apoptotic signalling pathways, leading to improved cognitive function and attenuation of neurodegeneration.
*eff↑, Based on their results, the authors suggest that treatment with α-LA would be a successful neuroprotective option in AD, at least as an adjuvant to standard treatment with acetylcholinesterase inhibitors.
*cAMP↑, The increase of cAMP caused by α-LA inhibits the release of proinflammatory cytokines, such as IL-2, IFN-γ, and TNF-α.
*IL2↓,
*INF-γ↓,
*TNF-α↓,
*SIRT1↑, Protein expression encoded by SIRT1 showed higher levels after α-LA treatment, especially in liver cells.
*SOD↑, antioxidant enzymes (SOD and GSH-Px) and malondialdehyde (MDA) were analysed by ELISA after 24 h of MCAO, which showed that the enzymatic activities were recovered and MDA was reduced in the α-LA-treated groups i
*GPx↑,
*MDA↓,
*NRF2↑, The ratio of nucleus/cytoplasmic Nrf2 was higher in the α-LA group 40 mg/kg, indicating that the activation of this factor also occurred in a dose-dependent manner

3547- ALA,    Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration
- Review, AD, NA - Review, Park, NA
*memory↑, a number of preclinical studies showing beneficial effects of LA in memory functioning, and pointing to its neuroprotective potential effect
*neuroP↑,
*motorD↑, Improved motor dysfunction
*VitC↑, elevates the activities of antioxidants such as ascorbate (vitamin C), α-tocoferol (vitamin E) (Arivazhagan and Panneerselvam, 2000), glutathione (GSH)
*VitE↑,
*GSH↑,
*SOD↑, superoxide dismutase (SOD) activity (Arivazhagan et al., 2002; Cui et al., 2006; Militao et al., 2010), catalase (CAT) (Arivazhagan et al., 2002; Militao et al., 2010), glutathione peroxidase (GSH-Px)
*Catalase↑,
*GPx↑,
*5HT↑, ↑levels of neurotransmitters (dopamine, serotonin and norepinephrine) in various brain regions
*lipid-P↓, ↓ level of lipid peroxidation,
*IronCh↑, ↓cerebral iron levels,
*AChE↓, ↓ AChE activity, ↓ inflammation
*Inflam↓,
*GlucoseCon↑, ↑brain glucose uptake; ↑ in the total GLUT3 and GLUT4 in the old mice;
*GLUT3↑,
*GLUT4↑,
NF-kB↓, authors showed that LA inhibited the stimulation of nuclear factor-κB (NF-κB)
*IGF-1↑, LA restored the parameters of total homocysteine (tHcy), insulin, insulin like growth factor-1 (IGF-1), interlukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Mahboob et al. (2016), analyzed the effects of LA in AlCl3- model of neurodegeneration,
*IL1β↓,
*TNF-α↓, Suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α) followed inhibition of cleaved caspase-3
*cognitive↑, demonstrating its capacity in ameliorating cognitive functions and enhancing cholinergic system functions
*ChAT↑, LA treatment increased the expression of muscarinic receptor genes M1, M2 and choline acetyltransferase (ChaT) relative to AlCl3-treated group.
*HO-1↑, R-LA and S-LA also enhanced expression of genes related to anti-oxidative response such as heme oxygenase-1 (HO-1) and phase II detoxification enzymes such as NAD(P)H:Quinone Oxidoreductase 1 (NQO1).
*NQO1↑,

3546- ALA,    Cognitive and Mood Effect of Alpha-Lipoic Acid Supplementation in a Nonclinical Elder Sample: An Open-Label Pilot Study
- Study, AD, NA
*antiOx↑, (ALA), a known antioxidant compound abundant in vegetables and animal tissues, in reducing oxidative stress in the aging brain and preventing cognitive decline.
*ROS↓,
*cognitive∅, no statistically significant effects either on cognitive function, executive function, or mood were found
*lipid-P↓, ALA has been shown to reduce lipid peroxidation and increase the activity of antioxidant molecules in different areas of the brain of experimental animals
*memory↑, ALA has been suggested to improve memory by increasing the activity of choline acetyltransferase (ChAT)
*ChAT↑,
*Acetyl-CoA↑, a crucial step in the biosynthesis of acetylcholine, in the hippocampi of treated rats
*Aβ↓, ALA administration can inhibit the formation of beta-amyloid fibrils and their expansion, thus exerting a direct effect on a known mechanism involved in neurodegenerative diseases
*BioAv↑, ALA is abundantly present in vegetables and animal tissues [17], is promptly bioavailable, and has no known toxic effects on animals and human subjects
*BBB↑, ALA has been demonstrated to successfully cross the blood–brain barrier in animal models
*toxicity∅, and no collateral effects have been observed at the oral daily doses currently employed as supplements (from 50 to 2400 mg/day)

3545- ALA,    Potential therapeutic effects of alpha lipoic acid in memory disorders
- Review, AD, NA
*neuroP↑, potential therapeutic effects for the prevention or treatment of neurodegenerative disease
*Inflam↓, ALA is able to regulate inflammatory cell infiltration into the central nervous system and to down-regulate VCAM-1 and human monocyte adhesion to epithelial cells
*VCAM-1↓, down-regulate vascular cell adhesion molecule-1 (VCAM-1) and the human monocyte adhesion to epithelial cells
*5HT↑, ALA is able to improve the function of the dopamine, serotonin and norepinephrine neurotransmitters
*memory↑, scientific evidence shows that ALA possesses the ability to improve memory capacity in a number of experimental neurodegenerative disease models and in age-related cognitive decline in rodents
*BioAv↝, Between 27 and 34% of the oral intake is available for tissue absorption; the liver is one of the main clearance organs on account of its high absorption and storage capacity
*Half-Life↓, The plasma half-life of ALA is approximately 30 minutes. Peak urinary excretion occurs 3-6 hours after intake.
*NF-kB↓, As an inhibitor of NF-κβ, ALA has been studied in cytokine-mediated inflammation
*antiOx↑, In addition to the direct antioxidant properties of ALA, some studies have shown that both ALA and DHLA and a great capacity to chelate redox-active metals, such as copper, free iron, zinc and magnesium, albeit in different ways (
*IronCh↑, ALA is able to chelate transition metal ions and, therefore, modulate the iron- and copper-mediated oxidative stress in Alzheimer’s plaques
*ROS↓, iron and copper chelation with DHLA may explain the low level of free radical damage in the brain and the improvement in the pathobiology of Alzheimer’s Disease
*ATP↑, ALA may increase the mitochondrial synthesis of ATP in the brain of elderly rats, thereby increasing the activity of the mitochondrial enzymes
*ChAT↑, ALA may also play a role in the activation of the choline acetyltransferase enzyme (ChAT), which is essential in the anabolism of acetylcholine
*Ach↑,
*cognitive↑, One experimental study has shown that in rats that had been administered ALA there was an inversion in the cognitive dysfunction with an increase in ChAT activity in the hippocampus
*lipid-P↓, administration of ALA reduces lipid peroxidation in different areas of the brain and increases the activity of antioxidants such as ascorbate (vitamin C), α-tocopherol (vitamin E), glutathione,
*VitC↑,
*VitE↑,
*GSH↑,
*SOD↑, and also the activity of superoxide dismutase, catalase, glutathione-peroxidase, glutathione-reductase, glucose-6-P-dehydrogenase
*Catalase↑,
*GPx↑,
*Aβ↓, Both ALA and DHLA have been seen to inhibit the formation of Aβ fibrils

297- ALA,    Insights on the Use of α-Lipoic Acid for Therapeutic Purposes
- Review, BC, SkBr3 - Review, neuroblastoma, SK-N-SH - Review, AD, NA
PDH↑, ALA is capable of activating pyruvate dehydrogenase in tumor cells.
TumCG↓, ALA also significantly inhibited tumor growth in mouse xenograft model using BCPAP and FTC-133 cells
ROS↑, ALA is able to generate ROS, which promote ALA-dependent cell death in lung cancer [75], breast cancer [76] and colon cancer
AMPK↑,
EGR4↓,
Half-Life↓, Data suggests that ALA has a short half-life and bioavailability (about 30%)
BioAv↝,
*GSH↑, Moreover, it is able to increase the glutathione levels inside the cells, that chelate and excrete a wide variety of toxins, especially toxic metals from the body
*IronCh↑, The existence of thiol groups in ALA is responsible for its metal chelating abilities [14,35].
*ROS↓, ALA exerts a direct impact in oxidative stress reduction
*antiOx↑, ALA is being referred as the universal antioxidant
*neuroP↑, ALA has neuroprotective effects on Aβ-mediated cytotoxicity
*Ach↑, ALA show anti-dementia or anti-AD properties by increasing acetylcholine (ACh) production through activation of choline acetyltransferase, which increases glucose absorption
*lipid-P↓, ALA has multiple and complex effects in this way, namely scavenging ROS, transition metal ions, increasing the levels of reduced glutathione [59,63], scavenging of lipid peroxidation products
*IL1β↓, ALA downregulated the levels of the inflammatory cytokines IL-1B and IL-6 in SK-N-BE human neuroblastoma cells
*IL6↓,
TumCP↓, ALA inhibited cell proliferation, [18F]-FDG uptake and lactate formation and increased apoptosis in neuroblastoma cell lines Kelly, SK-N-SH, Neuro-2a and in the breast cancer cell line SkBr3.
FDG↓,
Apoptosis↑,
AMPK↑, ALA suppressed thyroid cancer cell proliferation and growth through activation of AMPK and subsequent down-regulation of mTOR-S6 signaling pathway in BCPAP, HTH-83, CAL-62 and FTC-133 cells lines.
mTOR↓,
EGFR↓, ALA inhibited cell proliferation through Grb2-mediated EGFR down-regulation
TumCI↓, ALA inhibited metastatic breast cancer cells migration and invasion, partly through ERK1/2 and AKT signaling
TumCMig↓,
*memory↑, Alzheimer’s Disease: ALA led to a marked improvement in learning and memory retention
*BioAv↑, Since ALA is poorly soluble, lecithin has been used as an amphiphilic matrix to enhance its bioavailability.
*BioAv↝, ALA were found to be considerably higher in adults with mean age greater than 75 years as compared to young adults between the ages of 18 and 45 years.
*other↓, ALA treatment has been recently studied by some clinical trials to explain its efficacy in preventing miscarriage
*other↝, 1800 mg of ALA or placebo were administrated orally every day, except during the period 2 days before to 4 days after administration of each dose of platinum to avoid potential interference with platinum’s antitumor effects
*Half-Life↓, Data shows a short half-life and bioavailability of about 30% of ALA due to mechanisms involving hepatic degradation, reduced ALA solubility as well as instability in the stomach.
*BioAv↑, ALA bioavailability is greatly reduced after food intake and it has been recommended that ALA should be admitted at least 2 h after eating or if taken before; meal should be taken at least 30 min after ALA administration
*ChAT↑, ALA show anti-dementia or anti-AD properties by increasing acetylcholine (ACh) production through activation of choline acetyltransferase, which increases glucose absorption
*GlucoseCon↑,

3687- Ash,    Role of Withaferin A and Its Derivatives in the Management of Alzheimer’s Disease: Recent Trends and Future Perspectives
- Review, AD, NA
*Aβ↓, neuroprotective potential of WA is mediated by reduction of beta-amyloid plaque aggregation, tau protein accumulation, regulation of heat shock proteins, and inhibition of oxidative and inflammatory constituents.
*tau↓,
*HSPs↝, WA inhibited Hsp90 [127] and induced Hsp 27 and Hsp70 expressions
*antiOx↑,
*ROS↓,
*Inflam↓,
*neuroP↑, confirming WA’s neuroprotective potency against AD.
*cognitive↑, In an AD model, cognitive defects induced by ibotenic acid that was significantly reversed by WA isolated from Ashwagandha root
*NF-kB↓, inhibited nuclear factor NF-κB activation
*HO-1↑, WA also increased the neuro-protective protein heme oxygenase-1, which is beneficial to AD prevention
*memory↑, WA additionally enhances memory [133], prevents Aβ production, reconstructs synapses, and regenerates axons
*AChE↓, WA Inhibits AChE and BuChE Activities
*BChE↓,
*ChAT↑, WA has an important role in AD by reversing the reduction in cholinergic markers such as choline acetyltransferase (ChAT) and acetylcholine
*Ach↑, WA increased the level of ACh, the amount of choline acetyltransferase (ChAT)

5425- ASTX,    Multiple roles of fucoxanthin and astaxanthin against Alzheimer's disease: Their pharmacological potential and therapeutic insights
- in-vivo, AD, NA
*neuroP↑, fucoxanthin and astaxanthin, natural carotenoids abundant in algae, has shown to possess neuroprotective properties through antioxidant, and anti-inflammatory characteristics in modulating the symptoms of AD.
*antiOx↑,
*Inflam↑,
*AChE↓, Fucoxanthin and astaxanthin exhibit anti-AD activities by inhibition of AChE, BuChE, BACE-1, and MAO, suppression of Aβ accumulation.
*BACE↓,
*MAOA↓,
*Aβ↓,
*memory↑, Recently, Che, Li (Che et al., 2018) reported that astaxanthin possessed memory enhancement.
*MDA↓, Astaxanthin, as an antioxidant, helps to reduce oxidative stress by lowering malondialdehyde (MDA) levels and increasing SOD activity by activation of the NrF2/HO-1 pathway
*SOD↑,
*NRF2↑,
*HO-1↑,
*NF-kB↓, astaxanthin showed NFκB inhibitory activity which caused the downregulation of BACE-1 expression, resulting in Aβ reduction
*GSK‐3β↓, astaxanthin dose-dependently attenuated the GSK-3β activity
*ChAT↑, astaxanthin could reduce neuroinflammation via reducing iNOS expression and spine loss on the hippocampal CA1 pyramidal neurons, and restoring the ChAT expression in the medial septal nucleus
*iNOS↓,
*ROS↓, astaxanthin treatment decreased the ROS production and enhanced the cell growth.
*BBB↑, Astaxanthin can attenuate neurological dysfunction because of its unique chemical structure and can cross the BBB to enter the brain tissue

3690- BM,    Neurocognitive Effect of Nootropic Drug Brahmi (Bacopa monnieri) in Alzheimer's Disease
- Review, AD, NA
*ROS↓, EBm promotes free radical scavenger mechanisms
*5LO↓, reduces lipoxygenase activity reducing lipid peroxidation, increases glutathione peroxidase and chelates iron.
*lipid-P↓,
*GPx↑,
*IronCh↑,
*neuroP↑, EBm was seen to protect the cholinergic neurons and reduce anticholinesterase activity comparable to donepezil, rivastigmine, and galantamine.
*AChE↓,
*memory↑, EBm improved the total memory score and maximum improvement was seen in logical memory and paired associate learning in humans and reversed phenytoin-induced memory impairment in experimental model.
*toxicity↓, Mild nausea and gastrointestinal upset are seen in humans.
*SOD↑, EBm was administered to the rats for 21 days. It showed increase in activity of enzymes SOD, CAT, and GPx in prefrontal cortex, hippocampus, and striatum. I
*Catalase↑,
*cognitive↑, administration in indicated doses may act as a remedy for age-associated memory and cognitive decline in AD.
*ChAT↑, OBX reduced cholinergic activity and hence also ChAT in hippocampus. Subsequent administration of EBm and tacrine to the substrate, however, reversed this effect
*Ach↑,
*BP↓, Brahmi decreased systolic and diastolic blood pressure without significantly affecting heart rate.

3703- Chol,    Alzheimer's disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities
- Human, AD, NA
*ChAT↑, CAT activity was significantly reduced, most severely in the temporal lobe, in patients with Alzheimer's disease (hence choline might increase it)

3624- Cro,    Crocus Sativus L. (Saffron) in Alzheimer's Disease Treatment: Bioactive Effects on Cognitive Impairment
- Review, AD, NA
*AChE↓, aqueous and methanolic saffron extract presented a moderate activity as AChE inhibitor (up to 30%),
*memory↑, f 50-200 mg/kg of crocin enhanced memory impairment
*cognitive↑, crocin (30 mg/kg) for 3 weeks significantly improved cognitive impairment caused by intracerebroventricular injection of STZ,
*MDA↑, improved cognitive tasks and produced a significant decrease of malondialdehyde (MDA) levels and increase of total thiol content and glutathione peroxidase (GPx) activity in STZ-lesioned rats
*Thiols↑,
*GPx↑,
*antiOx↑, crocetin is only one and strong antioxidant, providing protection in rescuing cell viability, blocking reactive oxygen species (ROS) production and reducing caspase-3 activation
*ROS↓, crocin can prevent oxidative stress damage to hippocampus, memory and learning impairments
*Casp3↓,
*neuroP↑, neuroprotective effects of crocin against AD
*SOD↑, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase,
*Ach↑,
*ChAT↑,
*BBB↑, shown that crocetin, able to pass through BBB, inhibits fibril Aβ formation,
*Aβ↓,
*tau↓, inhibitory effects of crocin on tau protein neurofibrillary tangles in AD.
*cognitive↑, (15 mg twice a day) or a capsule of placebo (two capsules a day) for 16 weeks. The results of this study indicated that saffron produces a significant improvement in cognitive performance
*Inflam↓, anticholinergic, anti-inflammatory and antioxidant features

3631- Cro,    Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease
- in-vitro, AD, HT22 - in-vivo, AD, NA
*ROS↓, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells.
*Ca+2↓, crocin strongly inhibited the overload of Ca2+ compared with the l-Glu-damaged HT22 cells,
*BAX↓, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase-3
*BAD↓,
*Casp3↓,
*cognitive↑, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test,
*memory↑,
*Aβ↓, Crocin improved cognitive abilities of AD mice, and reduced Aβ deposition in their brains
*GPx↑, crocin was able to reduce the Aβ1-42 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase,
*SOD↑,
*ChAT↑,
*Ach↑,
*AChE↓, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice.
*ROS↓,
*p‑Akt↑, crocin upregulated the phosphorylation levels of Akt and mTOR in 24-h l-Glu-exposed cells.
*p‑mTOR↑,
*neuroP↑, crocin-mediated neuroprotection of l-Glu-damaged HT22 cells.

3576- CUR,    Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease
- Review, AD, NA
*Inflam↓, known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions.
*antiOx↑,
*memory↑,
*Aβ↓, curcumin prevents Aβ aggregation and crosses the blood-brain barrier,
*BBB↑,
*cognitive↑, curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD
*tau↓, curcumin's effect on inhibition of A and tau,copper binding ability, cholesterol lowering ability, anti-inflammatory and modulation of microglia, acetylcholinesterase (AChE) inhibition, antioxidant properties,
*LDL↓,
*AChE↓,
*IL1β↓, Curcumin reduced the levels of oxidized proteins and IL1B in the brains of APP mice
*IronCh↑, Curcumin binds to redox-active metals, iron and copper
*neuroP↑, Curcumin, a neuroprotective agent, has poor brain bioavailability.
*BioAv↝,
*PI3K↑, They found that curcumin significantly upregulates phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor E2-related factor-2 (Nrf2), heme oxygenase 1, and ferritin expression
*Akt↑,
*NRF2↑,
*HO-1↑,
*Ferritin↑,
*HO-2↓, and that it significantly downregulates heme oxygenase 2, ROS, and A40/42 expression.
*ROS↓,
*Ach↑, significant increase in brain ACh, glutathione, paraoxenase, and BCL2 levels with respect to untreated group associated with significant decrease in brain AChE activity,
*GSH↑,
*Bcl-2↑,
*ChAT↑, nvestigation revealed that the selected treatments caused marked increase in ChAT positive cells.

3714- FA,    Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer's Disease: A Narrative Review
- Review, AD, NA
*antiOx↑, antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy.
*Inflam↓,
*neuroP↑, neuroprotective strategy against AD due to its promising antioxidant and anti-inflammatory properties.
*NF-kB↓, inhibition of the nuclear factor kappa-B (NF-κ B), a key mediator of proinflammatory cytokine signaling pathway, which promotes the synthesis of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), leading to neuroinflammation
*NLRP3↓, also inhibited the NLR pyrin domain-containing protein 3 (NLRP3) inflammasome
*iNOS↓, A down-regulation by ferulic acid of proinflammatory molecules, such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1),
*COX2↓,
*TNF-α↓,
*IL1β↓,
*VCAM-1↓,
*ICAM-1↓,
*p‑MAPK↓, Ferulic acid was also able to affect the mitogen activated protein kinases (MAPKs) pathway, by inhibiting the phosphorylation of MAPKs, including p38 and c-Jun N-terminal kinase (JNK)
*p38↓,
*JNK↓,
*IL6↓, reduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8) mRNA expression
*IL8↓,
*hepatoP↑, ferulic acid reduces the liver damage induced by acetaminophen
*RenoP↑, renal protective effects by enhancing the CAT activity and PPAR γ gene expression
*Catalase↑,
*PPARγ↑,
*ROS↓, it was able to scavenge free radicals, inhibit the generation of reactive oxygen species (ROS)
*Fenton↓, inhibit the generation of reactive oxygen species (ROS) through the Fenton reaction, acting as a chelator of metals (i.e., Fe and Cu)
*IronCh↑,
*SOD↑, increasing the activity of the antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymes
*MDA↓, lowering in the levels of malondialdehyde (MDA), a lipid peroxidation marker,
*lipid-P↓,
*NRF2↑, ferulic acid has been found associated to the modulation of several signaling pathways, and to an increased expression of the nuclear translocation of the transcription factor NF-E2-related factor (Nrf2)
*HO-1↑, Particularly, Nrf2 binds the antioxidant responsive element (ARE) in the promoter region of the heme oxygenase-1 (HO-1) gene,
*ARE↑,
*Bil↑, production of bilirubin, which acts as an efficient ROS scavenger, in human umbilical vein endothelial cells (HUVEC) under radiation-induced oxidative stress
*radioP↑,
*GCLC↑, HO-1 upregulation, an increased expression of other antioxidant genes, such as glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), and NADPH quinone oxidoreductase-1 (NQO1) were induced by ferulic
*GCLM↑,
*NQO1↑,
*Half-Life↝, highest plasma concentration varies greatly depending on the investigated species: it is reached at 24 min and 2 min after ingestion in humans and rats, respectively
*GutMicro↑, ferulic acid esterified forms have been shown to act as a prebiotic, since they stimulate the growth of eubacteria, such as Lactobacilli and Bifidobacteria, in the human gastrointestinal tract, so preserving the homeostasis of gut microbiota,
*Aβ↓, ferulic acid was able to inhibit the aggregation of Aβ25–35, Aβ1–40, and Aβ1–42 and to destabilize pre-aggregated Aβ.
*BDNF↑, up-regulation of brain-derived neurotrophic factor (BDNF) gene were observed after treatment with ferulic acid
*Ca+2↓, prevented membrane damage, scavenged free radicals, increased SOD activity, and decreased the intracellular free Ca2+ levels, lipid peroxidation, and the release of prostaglandin E2 (PGE2);
*lipid-P↓,
*PGE2↓,
*cognitive↑, highlighted that ferulic administration (0.002–0.005% in drinking water) for 28 days improved the trimethyltin-induced cognitive deficit: an increase in the choline acetyltransferase activity was hypothesized as a possible mechanism of action.
*ChAT↑,
*memory↑, Another study showed that ferulic acid, administered intragastrically (30 mg/kg) for 3 months, improved memory in the transgenic APP/PS1 mice, and reduced Aβ deposits,
*Dose↝, 4-week prospective, open-label trial, in which patients (n = 20) assumed daily Feru-guard® (3.0 g/day), was designed.
*toxicity↓, Salau et al. [130] did not find signs of toxicity of ferulic acid in hippocampal neuronal cell lines HT22 cells, thus concluding that the substance seems to be safe in healthy brain cells

3910- PS,    Neuroprotective Effect of Bean Phosphatidylserine on TMT-Induced Memory Deficits in a Rat Model
- in-vivo, AD, NA
*memory↑, Treatment with Bean-PS enhanced memory function in the Morris water maze (MWM) test.
*neuroP↑, Consistent with the behavioral results, treatment with Bean-PS diminished the damage to cholinergic cells in the hippocampus, in contrast to those of the TMT group
*GlucoseCon↑, The TMT+Bean-PS group showed elevated glucose uptake in the frontal lobe of the rat brain
*ChAT↑, Immunoreactivity of ChAT in the TMT + Bean-PS group was significantly increased in CA1

3948- Shank,    Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity in rat brain
- in-vivo, AD, NA
*AChE↓, Daily administration of CP (150 mg/kg) for 3 months along with aluminium chloride (50 mg/kg) decreased the elevated enzymatic activity of acetylcholine esterase and also inhibited the decline in Na(+)/K(+)ATPase activity which resulted from aluminium
*ChAT↑, Oral administration of CP preserved the mRNA levels of muscarinic receptor 1 (M1 receptor), choline acetyl transferase (ChAT) and Nerve Growth Factor-Tyrosine kinase A receptor (NGF-TrkA).
*NGF↑,
*CDK5↓, It also ameliorated the upregulated protein expression of cyclin dependent kinase5 (Cdk5) induced by aluminium.
*neuroP↑, , indicative of its neuroprotective effects.
*MDA↓, Data showed co-treatment of CP to alu- minium treated rats led to a significant reduction in MDA by ∼23% and protein carbonyl by ∼71% as compared to group II.

4215- SY,    Safflower yellow alleviates cognitive impairment in mice by modulating cholinergic system function, oxidative stress, and CREB/BDNF/TrkB signaling pathway
- in-vivo, NA, NA
*memory↑, SY could shorten the escape latency and the time of the first crossing platform in the mice with memory acquisition and memory consolidation impairments, and increase the platform crossing times.
*AChE↓, SY decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress markers (SOD, MDA, and GSH-PX) in scopolamine-induced mice
*ChAT↑,
*SOD↓,
*MDA↓,
*GPx↑,
*BDNF↑, SY could activated BDNF/TrkB/CREB signaling pathway and reduced neuronal damage.
*TrkB↑,
*CREB↑,
*ROS↓, SY can restore the function of the cholinergic system, inhibit oxidative stress

3557- TQ,    Thymoquinone protects against lipopolysaccharides-induced neurodegeneration and Alzheimer-like model in mice.
- in-vivo, AD, NA
*Inflam↓, Thymoquinone is a known anti-inflammatory agent with a strong antioxidant activity.
*antiOx↑,
*cognitive↑, LPS significantly impaired performance in the Y-maze and NORT and induced behavioural abnormalities, compared to control. These were all ameliorated by treatment with TQ (15-30mg/kg).
*TNF-α↓, TQ also significantly (P<0.05) reduced the concentration of LPS-induced TNF-α, IL-1β, AChE and expressions of amyloid-beta, microglia and β-secretase/mRNA in hippocampus and prefrontal cortex.
*IL1β↓,
*AChE↓,
*IL10↑, TQ increased IL-10/mRNA, ChaT, synaptophysin in hippocampus and PFC
*ChAT↑,
*Aβ↓, depleted synaptic protein and Aβ accumulation.

4317- VitB5,    Unraveling the molecular mechanisms of vitamin deficiency in Alzheimer's disease pathophysiology
- Review, AD, NA
*Ach↑, It synthesizes key biomolecules, including haemoglobin, acetylcholine, and cholesterol synthesis for cell membrane integrity.
*ROS↓, Its deficiency disrupts the TCA cycle, and promotes oxidative stress, neuroinflammation, tau hyperphosphorylation, and Aβ plaque formation, key attributes of AD.
*Inflam↓,
*p‑tau↓,
*Aβ↓,
*Acetyl-CoA↑, Its deficiency prevents the production of CoA, which reduces the levels of acetyl-CoA, impairing neurotransmitter synthesis, ATP production, and tricarboxylic acid cycle function, thereby disrupting neuronal survival and function
*ATP↑,
*ChAT↑, Vitamin B5 deficiency impairs acetylcholine biosynthesis by inhibiting choline acetyltransferase (ChAT), which catalyzes acetyl-CoA and choline conversion
*memory↑, Acetylcholine decline impairs memory, and vitamin B5 deficiency disrupts pathways dependent on CoA-derived acyl groups, impairing fatty acid synthesis and causing neuronal dysfunction


Showing Research Papers: 1 to 20 of 20

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 20

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,   FDG↓, 1,   PDH↑, 1,  

Cell Death ⓘ

Apoptosis↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 1,   TumCG↓, 1,  

Migration ⓘ

TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   EGR4↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   Half-Life↓, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,  
Total Targets: 16

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 12,   ARE↑, 1,   Bil↑, 1,   Catalase↑, 4,   Fenton↓, 1,   GCLC↑, 1,   GCLM↑, 1,   GPx↑, 7,   GSH↑, 6,   HO-1↑, 6,   HO-2↓, 1,   lipid-P↓, 8,   MDA↓, 5,   MDA↑, 1,   NQO1↑, 2,   NRF2↑, 7,   ROS↓, 16,   ROS↑, 1,   SOD↓, 1,   SOD↑, 8,   Thiols↑, 1,   VitC↑, 2,   VitE↑, 2,  

Metal & Cofactor Biology ⓘ

Ferritin↑, 1,   IronCh↑, 8,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 2,  

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↑, 3,   cAMP↑, 1,   CREB↑, 1,   GlucoseCon↑, 5,   LDL↓, 1,   PDH↑, 1,   PDKs↓, 1,   PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↑, 1,   p‑Akt↑, 1,   BAD↓, 1,   BAX↓, 1,   Bcl-2↑, 1,   Casp3↓, 3,   Casp9↓, 1,   iNOS↓, 3,   JNK↓, 1,   p‑MAPK↓, 1,   p38↓, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 11,   other↓, 1,   other↝, 1,  

Protein Folding & ER Stress ⓘ

HSPs↝, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,   IGF-1↑, 1,   p‑mTOR↑, 1,   PI3K↑, 1,  

Migration ⓘ

5LO↓, 1,   Ca+2↓, 3,   CDK5↓, 1,   VCAM-1↓, 3,  

Angiogenesis & Vasculature ⓘ

Hif1a↑, 1,   VEGF↑, 1,  

Barriers & Transport ⓘ

BBB↑, 6,   GLUT3↑, 2,   GLUT4↑, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   ICAM-1↓, 1,   IL10↑, 1,   IL1β↓, 6,   IL2↓, 1,   IL6↓, 3,   IL8↓, 1,   INF-γ↓, 1,   Inflam↓, 11,   Inflam↑, 1,   NF-kB↓, 4,   PGE2↓, 2,   TNF-α↓, 5,  

Synaptic & Neurotransmission ⓘ

5HT↑, 2,   AChE↓, 10,   BChE↓, 1,   BDNF↑, 2,   ChAT↑, 20,   MAOA↓, 1,   NGF↑, 1,   tau↓, 3,   p‑tau↓, 2,   TrkB↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 11,   BACE↓, 1,   NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 4,   BioAv↝, 3,   Dose↝, 1,   eff↑, 1,   Half-Life↓, 3,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

Bil↑, 1,   BP↓, 1,   Ferritin↑, 1,   GutMicro↑, 1,   IL6↓, 3,  

Functional Outcomes ⓘ

AntiAge↑, 1,   AntiCan↑, 1,   cardioP↑, 1,   cognitive↑, 14,   cognitive∅, 1,   hepatoP↑, 2,   memory↑, 16,   motorD↑, 1,   neuroP↑, 15,   radioP↑, 1,   RenoP↑, 1,   toxicity↓, 2,   toxicity∅, 1,   Weight↓, 1,  
Total Targets: 115

Scientific Paper Hit Count for: ChAT, Choline acetyltransferase
7 Alpha-Lipoic-Acid
2 Crocetin
1 Ashwagandha(Withaferin A)
1 Astaxanthin
1 Bacopa monnieri
1 Choline
1 Curcumin
1 Ferulic acid
1 Phosphatidylserine
1 Shankhpushpi
1 Safflower yellow
1 Thymoquinone
1 Vitamin B5,Pantothenic Acid
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

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