Mitochondrial plasticity and synaptic plasticity crosstalk; in health and Alzheimer's disease

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(8)

Published: Aug. 1, 2024

Abstract Synaptic plasticity is believed to underlie the cellular and molecular basis of memory formation. Mitochondria are one main organelles involved in metabolism energy maintenance as plastic that change morphologically functionally response needs regulate synaptic function through multiple mechanisms, including ATP generation, calcium homeostasis, biogenesis. An increased neuronal activity enhances efficiency, during which mitochondria's spatial distribution morphology significantly. These build up pre‐and postsynaptic zones produce ATP, necessary for several processes like neurotransmitter release recycling. also homeostasis by buffering intracellular calcium, ensures proper activity. Furthermore, mitochondria presynaptic terminal have distinct morphological properties compared dendritic or mitochondria. This specialization enables precise control plasticity. Mitochondrial dysfunction has been linked failure many neurodegenerative disorders, Alzheimer's disease (AD). In AD, malfunctioning cause delays vesicle recycling, ionic gradient imbalances, mostly failure. review emphasizes mitochondrial plasticity's contribution function. It explores profound effect malfunction on focusing provides an overview how they sustain health under normal conditions their contributes diseases, highlighting potential a therapeutic target such conditions.

Language: Английский

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Neuroprotective Effects of Olive Oil: A Comprehensive Review of Antioxidant Properties

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 762 - 762

Published: June 24, 2024

Neurodegenerative diseases are a significant challenge to global healthcare, and oxidative stress plays crucial role in their development. This paper presents comprehensive analysis of the neuroprotective potential olive oil, with primary focus on its antioxidant properties. The chemical composition including key antioxidants, such as oleuropein, hydroxytyrosol, oleocanthal, is systematically examined. mechanisms by which these compounds provide neuroprotection, counteracting damage modulating pathways, explored. efficacy oil evaluated synthesizing findings from various sources, vitro studies, animal models, clinical trials. integration into dietary patterns, particularly Mediterranean diet, broader implications neurodegenerative disease prevention also discussed. challenges translating preclinical applications acknowledged future research directions proposed better understand mitigating risk conditions. review highlights not only component, but promising candidate preventive neurology, advocating for further investigation context diseases.

Language: Английский

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The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer’s Disease Etiopathology

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1208 - 1208

Published: Oct. 8, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and it currently the seventh leading cause of death worldwide. It characterized by extracellular aggregation amyloid β-peptide (Aβ) into oligomers fibrils that synaptotoxicity neuronal death. Aβ exhibits dual role in promoting oxidative stress inflammation. This review aims to unravel intricate connection between these processes their contribution AD progression. The delves AD, focusing on involvement metals, mitochondrial dysfunction, biomolecule oxidation. distinct yet overlapping concept nitro-oxidative also discussed, detailing roles nitric oxide, perturbations, cumulative impact production neurotoxicity. Inflammation examined through astroglia microglia function, elucidating response within brain. blood-brain barrier oligodendrocytes are considered context pathophysiology. We current diagnostic methodologies emerging therapeutic strategies aimed at mitigating inflammation, thereby offering potential treatments for halting or slowing comprehensive synthesis underscores pivotal bridging advancing our understanding informing future research treatment paradigms.

Language: Английский

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Alzheimer’s Disease: Exploring Pathophysiological Hypotheses and the Role of Machine Learning in Drug Discovery

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1004 - 1004

Published: Jan. 24, 2025

Alzheimer’s disease (AD) is a major neurodegenerative dementia, with its complex pathophysiology challenging current treatments. Recent advancements have shifted the focus from traditionally dominant amyloid hypothesis toward multifactorial understanding of disease. Emerging evidence suggests that while amyloid-beta (Aβ) accumulation central to AD, it may not be primary driver but rather part broader pathogenic process. Novel hypotheses been proposed, including role tau protein abnormalities, mitochondrial dysfunction, and chronic neuroinflammation. Additionally, gut–brain axis epigenetic modifications gained attention as potential contributors AD progression. The limitations existing therapies underscore need for innovative strategies. This study explores integration machine learning (ML) in drug discovery accelerate identification novel targets candidates. ML offers ability navigate AD’s complexity, enabling rapid analysis extensive datasets optimizing clinical trial design. synergy between these themes presents promising future more effective

Language: Английский

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Single Cell Landscape of Sex-specific Drivers of Alzheimer’s Disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Background Sex differences in Alzheimer’s disease (AD) have been documented for decades, and many sex-specific molecular contributors to AD discovered through bulk omics analysis of brain tissues. RNA sequencing (RNAseq) at single cell resolution provides an opportunity characterize transcript associations with a type-specific matter. Here, we investigated gene expression neuropathology cognitive manifestation (endophenotypes) leveraging large single-nucleus transcriptomic dataset consisting 1.64 million nuclei from dorsolateral prefrontal cortex (DLPFC) tissue 424 unique donors the Religious Orders Study Memory Aging Project (ROS/MAP; Knowledge Portal syn2580853). Methods ROS/MAP RNAseq data (snRNA-seq) were processed rigorous pipeline. In total, eight major types DLPFC identified. We first performed sex-stratified sex-interaction association analyses by fitting negative binomial mixed models relation β-amyloid load (Aβ), paired helical filament tau tangle density (tau), global performance last visit, longitudinal trajectory. then conducted gene-set enrichment identify functional signaling pathways enriched associations. Lastly, compared differential patterns intercellular communication profiles between sexes diagnostic groups among types. For replication, examined using snRNA-seq derived tissue-derived independent set 84 The Seattle Disease Brain Cell Atlas (SEA-AD) study. Results 68% participants female, 52% diagnosed dementia. identified several disease-dependent or sex-dependent subpopulations. Then 2,660 involving 2,110 genes Aβ (51%), (21%), (29%). 60% female-specific Aβ, 49% male-specific tau. vast majority (93%) female protective neurons, most (76%) risk glial cells. Nine replicated SEA-AD cohort, including ADGRV1 OR3A3 Aβ; IFI27L1 , LYRM1 STAP2 TSTD2 tau; PDYN cognition; TMEM50B decline. All except observed neurons. Furthermore, preponderance neurons was also recapitulated cohort. Sex-specific immune, inflammation, damage-related stress response pathways, microglia presented pathways. Finally, six ITGB1-mediated microglia-specific incoming signals that may play role accumulation. Conclusion Our study highlights transcriptome-wide, single-cell landscape delineate full scope associations, expression, pathway, cell-cell network changes each type, while identifying replicating help direct future mechanistic studies.

Language: Английский

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Bioassay-guided isolation of acetylcholinesterase and butyrylcholinesterase inhibitors from Horsfieldia tomentosa fruits (Myristicaceae)

Phytochemistry Letters, Journal Year: 2025, Volume and Issue: 65, P. 133 - 140

Published: Jan. 21, 2025

Language: Английский

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Neuroprotective insights into epigallocatechin gallate (EGCG) for neurodegenerative disorders

Exploration of neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Neurodegenerative disorders, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are among the most significant health concerns worldwide, characterized by neuronal dysfunction, oxidative stress, neuroinflammation, protein misfolding. Epigallocatechin gallate, a green tea polyphenol, has been reported to possess multifaceted neuroprotective properties. It reduces stress through free radical scavenging, activation of antioxidant enzymes, stabilization mitochondrial function. also inhibits neuroinflammation modulation key signaling pathways. suppresses amyloid-beta aggregation in Alzheimer’s alpha-synuclein fibrillation thus attenuating toxic accumulation. Its activity induction autophagy promotion synaptic plasticity supports survival However, low bioavailability metabolic instability hinder its translation into clinic. Strategies nanoparticle encapsulation, structural modifications, combination therapies being explored overcome these challenges. Future research could establish epigallocatechin gallate as viable candidate for managing neurodegenerative disorders.

Language: Английский

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Mechanistic Insights into the Neuroprotective Potential of Aegle marmelos (L.) Correa Fruits against Aβ-Induced Cell Toxicity in Human Neuroblastoma SH-SY5Y Cells

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 489 - 489

Published: March 28, 2025

Background/Objectives: Amyloid-β (Aβ) plaque accumulation, oxidative stress, and cholinergic dysfunction are hallmarks of Alzheimer’s disease (AD), a neurodegenerative disability that progresses over time, ultimately resulting in the loss neurons. The side effects limitations current synthetic drugs have shifted attention toward natural alternatives. This study investigates ethanolic extract Aegle marmelos (L.) Corrêa fruits for their antioxidant, AChE-inhibitory, anti-amyloidogenic properties, as well neuroprotective against amyloid beta-peptide (Aβ1–42). Methods: Phytochemical constituents were identified through HR-LCMS analysis antioxidant (DPPH, FRAP) activities (AChE inhibition, ThT binding, MTT assay, ROS reduction, MMP restoration, AD-related gene expression via qRT-PCR) assessed using SHSY-5Y neuroblastoma cells. Results: revealed existence flavonoids, phenols, other bioactive substances. In vitro assays demonstrated strong AChE-inhibitory activities, while binding assay showed protection amyloid-β aggregation. exhibited no cytotoxicity cells, even at concentration 500 μg/mL, whereas Aβ1–42 20 μM induced significant cytotoxicity. Co-treatment with (10 μM) improved cell viability (˃50%) reduced levels. Additionally, restored mitochondrial membrane potential treated highlighting its role preserving function. Conclusions: These findings suggest A. serve powerful source antioxidants, AChE inhibitors, agents, positioning them compelling option AD treatment.

Language: Английский

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Unraveling the cGAS-STING pathway in Alzheimer’s disease: A new Frontier in neuroinflammation and therapeutic strategies

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Shedding light on microglial dysregulation in Alzheimer’s disease: exploring molecular mechanisms and therapeutic avenues

Inflammopharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Language: Английский

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