Molecular Signaling Pathways of Quercetin in Alzheimer’s Disease: A Promising Arena DOI Creative Commons
Mansour Alsaleem, Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 45(1)

Published: Dec. 24, 2024

Abstract Alzheimer’s disease (AD) is a neurodegenerative characterized by cognitive impairment and memory deficit. Even with extensive research studies, presently, there no effective treatment for the management of AD. Besides, most drugs used in AD did not avert neuropathology, still progressive status. For example, acetyl cholinesterase inhibitors are associated many adverse effects, such as insomnia nightmares. As well, acetylcholinesterase augment cholinergic neurotransmission leading to development effects related high acetylcholine level, salivation, rhinorrhea, vomiting, loss appetite, seizure. Furthermore, tacrine has poor bioavailability causes hepatotoxicity. These commonly do manage original those reasons, natural products were repurposed diseases. It been shown that phytochemicals produce neuroprotective against progression diseases different mechanisms, including antioxidant anti-inflammatory effects. Quercetin (QCN) reported exert an effect other lessening oxidative stress. In this review, electronic databases PubMed, Scopus, Web Science searched possible relevant studies article linking QCN on Findings from review highlighted mechanistic signaling pathways regarding Nevertheless, precise molecular mechanism was completely clarified. Consequently, aims discuss

Language: Английский

Amyloid-β and heart failure in Alzheimer’s disease: the new vistas DOI Creative Commons
Hayder M. Al‐kuraishy, Ghassan M. Sulaiman, Hamdoon A. Mohammed

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 4, 2025

Alzheimer’s disease (AD) is the most common cause of dementia and represents 75% all types. AD neuropathology due to progressive deposition extracellular amyloid-beta (A β ) peptide intracellular hyperphosphorylated tau protein. The accumulated Aβ forms amyloid plaques, while protein neurofibrillary tangles (NFTs). Both plaques NFTs are hallmarks neuropathology. fundamental mechanism involved in pathogenesis still elusive, although more conceivable theory. Aβ-induced neurodegeneration associated neuroinflammation, oxidative stress, endoplasmic reticulum stress (ER), mitochondrial dysfunction contribute development cognitive impairment dementia. Of note, not only originated from brain but also produced peripherally and, via blood–brain barrier (BBB), can accumulate result AD. It has been shown that cardiometabolic conditions such as obesity, type 2 diabetes (T2D), heart failure (HF) regarded possible risk factors for other types dementia, vascular HF-induced chronic cerebral hypoperfusion, inflammation induce progression Interestingly, a systemic causes which turn affects peripheral organs, including heart. through deranged BBB be transported into circulation heart, leading HF. These findings suggest close relationship between However, exact AD-induced HF fully elucidated. Therefore, this review aims discuss link regarding potential role

Language: Английский

Citations

4
Decremental response in patients with amyotrophic lateral sclerosis during repetitive nerve stimulation and its relationships with impaired homeostasis DOI Creative Commons
Jinghong Zhang, Yang Li, Qiang Shi

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 7, 2025

Previous studies have suggested that neuromuscular junction (NMJ) denervation plays a critical role in amyotrophic lateral sclerosis (ALS). Repetitive nerve stimulation (RNS) has been used as technique to test transmission, but the sensitivity and stability of its parameters not investigated patients with ALS. In addition, impact impaired homeostasis on NMJ ALS remains unclear. A total 421 were enrolled. Data their clinical, biochemical electrophysiological indicators divided into training set (collected from June 2019 2022) July 2022 2023). The coefficient variation (CV) was assess extent variability. Stepwise regression independent variable selection model building. ALS, area decrement had higher rate abnormal result lower CV than amplitude decrement. No significant difference found when first compound muscle action potential (CMAP) compared either fourth or fifth one. Moreover, multivariate analysis suggests high-density lipoprotein cholesterol (HDL-C) greatest decremental response, followed by serum uric acid (UA) forced vital capacity (FVC). Females larger range males. During RNS test, assessing significantly enhances our ability detect impairment transmission Independent factors contributing response need be considered drug development clinical trials targeting

Language: Английский

Citations

0
Role of mitogen-activated protein kinase inhibitors in Alzheimer's disease: Rouge of brain kinases DOI Creative Commons

Suad Hamdan Almasoudi,

Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 224, P. 111296 - 111296

Published: March 10, 2025

Alzheimer's disease (AD) is the chief cause of dementia and related mortality worldwide due to progressive accumulation amyloid peptide (Aβ) hyperphosphorylated tau protein. These neuropathological changes lead cognitive impairment memory dysfunction. Notably, most Food drug Administration (FDA) approved anti-AD medications such as tacrine donepezil are engaged with symptomatic relief but do not reverse underlying AD neuropathology. Therefore, searching for new advisable. It has been shown that inflammatory signaling pathways mitogen-activated protein kinases (MAPK) intricate Aβ neuropathology in AD. In addition, inhibition brain MAPK plays a critical role mitigating dysfunction early-onset Though, fundamental mechanisms beneficial effects inhibitors were fully explained. this review aims discuss potential molecular

Language: Английский

Citations

0
The neuroprotective role of Humanin in Alzheimer's disease: The molecular effects DOI Creative Commons
Saad Misfer Alqahtani, Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177510 - 177510

Published: March 1, 2025

Humanin (HN) is an endogenous micropeptide also known as a mitochondria-derived peptide. It has neuroprotective effect against Alzheimer's disease (AD) and other neurodegenerative diseases by improving hippocampal acetylcholine attenuating the development of oxidative stress associated neurotoxicity. HN protects neuron from toxic effects amyloid beta (Aβ). regarded biomarker mitochondrial stress. Interestingly, aging reduces brain expression HN, leading to cognitive impairment elevating risk neurodegeneration, including AD. However, in old subjects AD patients, circulating levels increase compensatory mechanism reduce neurodegeneration dysfunction Conversely, studies demonstrated reduction These findings indicated controversial points regarding precise mechanistic role Therefore, aim this review was discuss exact neuropathology molecular mechanisms

Language: Английский

Citations

0
Atorvastatin, simvastatin, rosuvastatin and Amyotrophic lateral sclerosis establishing cause and effect DOI
Min Li, Yaping Li, Xuping Yang

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Abstract Background/Objectives: Statins are drugs that lower lipids levels, and widely used to reduce the risk of cardiovascular disease. Previous observational studies experimental investigations have indicated statin is associated with Amyotrophic Lateral Sclerosis (ALS). However, causal relationship remains unclear.The present study employs a two-sample Mendelian randomization (MR) analysis investigate between atorvastatin, simvastatin, rosuvastatin ALS at nenetic level. Methods: The utilized genome-wide association (GWAS) based on single-nucleotide polymorphisms (SNPs) for three statins (atorvastatin, rosuvastatin), encompassing data 462,933 participants obtained from UK Biobank, 80,610 individuals in genetic level European. investigation effects implemented five methods: inverse variance weighting (IVW), MR-Egger regression, wighted median, simple mode, weighted mode. To detect horizontal pleiotropy, intercept test MR pleiotropy residual sum outlier (MR-PRESSO) global were employed. Instrument heterogeneity was evaluated by Cochran’s Q statistics. Sensitivity performed via leave-one-out method. Results: suggest potential use ALS, odds ratio (OR) confidence interval (CI) providing further insight into strength this association. results estimate revealed significantly elevated atorvastatin (OR = 16.93, 95% CI: 5.42-52.89, p 1.13E-06), simvastatin 5.05, 2.92-8.75, 7.49E-09), 6.93E+5, 247.72-1.94E+9, 8.97-05). sensitivity highlighted stability reliability casual results. Conclusions: The provided evidence rosuvastatin) increased ALS. Given drug's effectiveness side effects, higher should be cautious about th statins. Further robust reserch needed confirm results, findings will provide valuable guidance drug patients.

Language: Английский

Citations

0
Targeting of AMPK/MTOR signaling in the management of atherosclerosis: Outmost leveraging DOI
Hayder M. Al‐kuraishy, Ghassan M. Sulaiman, Mayyadah H. Mohsin

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 309, P. 142933 - 142933

Published: April 8, 2025

Language: Английский

Citations

0
Targeting of PP2 A/GSK3β/PTEN Axis in Alzheimer Disease: The Mooting Evidence, Divine, and Devil DOI Creative Commons
Saad Misfer Alqahtani,

Hayder M Al-Kuraishy,

Ali I. Al‐Gareeb

et al.

Cellular and Molecular Neurobiology, Journal Year: 2025, Volume and Issue: 45(1)

Published: April 18, 2025

Abstract Alzheimer disease (AD) is a progressive neurodegenerative of the brain due to extracellular accumulation Aβ. In addition, intracellular hyperphosphorlyated tau protein which form neurofibrillary tangle (NFT) associated with neuronal injury and development AD. Aβ NFTs interact together induce inflammation oxidative stress further neurodegeneration in The exact relationship between tau, two proteins that accumulate within these lesions, has proven elusive. A growing body work supports notion may directly or indirectly accelerate formation. can adversely affect distinct molecular cellular pathways, thereby facilitating phosphorylation, aggregation, mislocalization, accumulation. drive pathology by activating specific kinases, providing straightforward mechanism enhance hyperphosphorylation NFT Many signaling pathways such as phosphatase 2A (PP2A), glycogen synthase kinase 3β (GSK3β), tensin homologue (PTEN) are intricate AD neuropathology. PP2A involved dephosphorylation deregulated AD, correlated cognitive impairment. PTEN critical regulator growth, survival, development, improving synaptic plasticity axonal regeneration. Nevertheless, mutated impairment inhibiting expression activity PP2A. Furthermore, dysregulation GSK3β affects Aβ, other pathogenesis Therefore, there close interaction among GSK3β, PTEN, exaggerates neuropathology activates PTEN. These findings specified related PP2A, modulation single component this axis not produce an effective effect against Modulation metformin statins reduce review aims discuss role GSK3β/PTEN/PP2A how targeting therapeutic strategy management conclusion, inhibition activation be more suitable than pathway. Metformin attenuate progression Graphical

Language: Английский

Citations

0
Safety assessment of ezetimibe: real-world adverse event analysis from the FAERS database DOI
Yuchen Han, Siyuan Cheng,

Jinzheng He

et al.

Expert Opinion on Drug Safety, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 21, 2024

Ezetimibe is known for its lipid-lowering safety and tolerability, but real-world adverse effects have not been fully evaluated. In this study, events associated with ezetimibe were investigated using the FAERS database period 2004 to 2023.

Language: Английский

Citations

1
Statins for vascular dementia: A hype or hope DOI Creative Commons

Haroon Raja,

Hayder M. Al‐kuraishy, Mustafa M Shokr

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 567, P. 45 - 55

Published: Dec. 31, 2024

Language: Английский

Citations

1
Molecular Signaling Pathways of Quercetin in Alzheimer’s Disease: A Promising Arena DOI Creative Commons
Mansour Alsaleem, Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 45(1)

Published: Dec. 24, 2024

Abstract Alzheimer’s disease (AD) is a neurodegenerative characterized by cognitive impairment and memory deficit. Even with extensive research studies, presently, there no effective treatment for the management of AD. Besides, most drugs used in AD did not avert neuropathology, still progressive status. For example, acetyl cholinesterase inhibitors are associated many adverse effects, such as insomnia nightmares. As well, acetylcholinesterase augment cholinergic neurotransmission leading to development effects related high acetylcholine level, salivation, rhinorrhea, vomiting, loss appetite, seizure. Furthermore, tacrine has poor bioavailability causes hepatotoxicity. These commonly do manage original those reasons, natural products were repurposed diseases. It been shown that phytochemicals produce neuroprotective against progression diseases different mechanisms, including antioxidant anti-inflammatory effects. Quercetin (QCN) reported exert an effect other lessening oxidative stress. In this review, electronic databases PubMed, Scopus, Web Science searched possible relevant studies article linking QCN on Findings from review highlighted mechanistic signaling pathways regarding Nevertheless, precise molecular mechanism was completely clarified. Consequently, aims discuss

Language: Английский

Citations

0