Metformin Improves Spatial Memory and Reduces Seizure Severity in a Rat Model of Epilepsy and Alzheimer’s Disease comorbidity via PI3K/Akt Signaling Pathway

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

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Exercise‐induced signalling in alleviating neuronal insulin resistance

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Exercise contributes to a multitude of positive changes within the body and brain with regard glucose homeostasis, insulin sensitivity, synaptic plasticity, neuroprotection neurogenesis, among other effects. It provides non-pharmaceutical alternative for addressing metabolic disorders in individuals type 2 diabetes, who also face an increased risk developing Alzheimer's disease. A number molecules are evoked upon exercise circulate through bloodstream, transmitting wide-reaching advantages exercise. The ensuing cross-talk has been shown improve conditions associated vast signalling network mediated by is currently being studied extensively its implications improving neuronal resistance, especially as bypass mechanism, major interest. Taking into account sirtuin 1/peroxisome proliferator-activated receptor γ co-activator 1-α, AMP-activated protein kinase, phosphoinositide 3-kinase/AKT, phospholipase C-γ brain-derived neurotrophic factor/tropomyosin kinase B many pathways cross-interactions involved, researching molecular characteristics mechanisms which it compensates hampered crucial future research.

Language: Английский

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Microvascular and cellular dysfunctions in Alzheimer’s disease: an integrative analysis perspective

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 9, 2024

Language: Английский

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Nanocurcumin prevents memory impairment, hippocampal apoptosis, Akt and CaMKII-α signaling disruption in the central STZ model of Alzheimer’s disease in rat

Behavioural Brain Research, Journal Year: 2024, Volume and Issue: 471, P. 115129 - 115129

Published: June 26, 2024

Language: Английский

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Breaking Barriers in Alzheimer’s Disease: the Role of Advanced Drug Delivery Systems

AAPS PharmSciTech, Journal Year: 2024, Volume and Issue: 25(7)

Published: Sept. 5, 2024

Language: Английский

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Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid and Tau P301L-Driven Pathomechanisms

Published: Feb. 19, 2024

Alzheimer's disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine or glucose-related pathways have been described through AD progression. Specifically, an alteration glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has observed areas from subjects. However, biological role GNPDA2 neurodegeneration remains unknown. Using mass-spectrometry, multiple interactors were identified human nasal epithelial cells (NECs) mainly involved intraciliary transport. Moreover, overexpression induced increment NEC proliferation rates, accompanied by transcriptomic alterations Type II interferon signalling cellular stress responses. In contrast, presence beta-amyloid mutated Tau-P301L GNPDA2-overexpressing NECs slow-down proliferative capacity parallel with disruption processing. The proteomic characterization transgenic zebrafish embryos demonstrated that interfered collagen biosynthesis and RNA/protein processing, without inducing additional changes axonal outgrowth defects nor neuronal cell death. humans, significant increase serum was across neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed-dementia, amyotrophic lateral sclerosis) (n=187). These data shed new light on GNPDA2-dependent mechanisms associated to process beyond route.

Language: Английский

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Integrated systems pharmacology, molecular docking, and MD simulations investigation elucidating the therapeutic mechanisms of BHD in Alzheimer’s disease treatment

Metabolic Brain Disease, Journal Year: 2024, Volume and Issue: 40(1)

Published: Nov. 18, 2024

Language: Английский

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The wake- and sleep-modulating neurons of the lateral hypothalamic area demonstrate a differential pattern of degeneration in Alzheimer’s disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 12, 2024

Background Sleep-wake dysfunction is an early and common event in Alzheimer’s disease (AD). The lateral hypothalamic area (LHA) regulates the sleep wake cycle through wake-promoting orexinergic neurons (Orx N ) sleep-promoting melanin-concentrating hormone or MCHergic (MCH ). These share close anatomical proximity with functional reciprocity. This study investigated LHA Orx MCH loss patterns AD individuals. Understanding degeneration pattern of these will be instrumental designing potential therapeutics to slow down progression remediate sleep-wake AD. Methods Postmortem human brain tissue from donors (across progressive stages) controls were examined using unbiased stereology. Formalin-fixed, celloidin-embedded sections stained Orx-A/MCH, p-tau (CP13), counterstained gallocyanin. MCH-positive without CP13 inclusions gallocyanin-stained considered for stereology counting. Additionally, we extracted RNA conventional techniques. We used customized Neuropathology Glia nCounter ® (Nanostring) panels gene expression. Wald statistical test was compare groups, genes differentially expressed when p-value <.05. Results observed a decline alongside relative preservation . decreased by 58% (p=.03) Braak stages (BB) 1-2 further declined 81% BB 5-6. Conversely, demonstrated non-statistical significant (27%, p=.1088) 6. increase (DEGs), starting glial profile changes BB2. While observed, Orx-related showed upregulation 3-4 compared 0-1. GO KEGG terms related neuroinflammatory pathways mainly enriched. Conclusions To date, represents first neuronal population die preceding LC neurons. MCHN shows resilience accumulation across stages. initial correlates specific neuroinflammation, changes, overexpression HCRT, possibly due hyperexcitation following compensation mechanisms. Interventions preventing inhibiting could prevent and, perhaps, disease.

Language: Английский

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Rlip76 in Ageing and Alzheimer’s Disease: Focus on Oxidative Stress and Mitochondrial Mechanisms

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 103, P. 102600 - 102600

Published: Nov. 30, 2024

Language: Английский

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Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 394 - 394

Published: March 25, 2024

Alzheimer’s disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine- or glucose-related pathways have been described through AD progression. Specifically, an alteration glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has observed areas subjects. However, biological role GNPDA2 neurodegeneration remains unknown. Using mass spectrometry, multiple interactors were identified human nasal epithelial cells (NECs) mainly involved intraciliary transport. Moreover, overexpression induced increment NEC proliferation rates, accompanied by transcriptomic alterations Type II interferon signaling cellular stress responses. In contrast, presence beta-amyloid mutated Tau-P301L GNPDA2-overexpressing NECs slowdown proliferative capacity parallel with disruption processing. The proteomic characterization transgenic zebrafish embryos demonstrated that interfered collagen biosynthesis and RNA/protein processing, without inducing additional changes axonal outgrowth defects neuronal cell death. humans, significant increase serum was across neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed dementia amyotrophic lateral sclerosis) (n = 215). These data shed new light on GNPDA2-dependent mechanisms associated process beyond hexosamine route.

Language: Английский

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