Recent advancement in understanding of Alzheimer's disease: Risk factors, subtypes, and drug targets and potential therapeutics

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102476 - 102476

Published: Aug. 31, 2024

Language: Английский

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Advances in the Study of Necroptosis in Vascular Dementia: Focus on Blood–Brain Barrier and Neuroinflammation

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

ABSTRACT Background Vascular dementia (VaD) includes a group of brain disorders that are characterized by cerebrovascular pathology.Neuroinflammation, disruption the blood–brain barrier (BBB) permeability, white matter lesions, and neuronal loss all significant pathological manifestations VaD play key role in disease progression. Necroptosis, also known asprogrammed necrosis, is mode programmed cell death distinct from apoptosis closely associated with ischemic injury neurodegenerative diseases. Recent studies have shown necroptosis exacerbates BBB destruction, activates neuroinflammation, promotes loss, severely affects prognosis. Results Conclusions In this review, we outline roles its molecular mechanisms process VaD, particular focus on modulating neuroinflammation exacerbating permeability elaborate regulatory centrally involved cells mediated tumor necrosis factor‐α VaD. We analyze possibility specific strategy targeting would help inhibit destruction With necroptosis, study delved into impact changes prognosis to provide new treatment ideas.

Language: Английский

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Vascular Impairment, Muscle Atrophy, and Cognitive Decline: Critical Age-Related Conditions

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 2096 - 2096

Published: Sept. 13, 2024

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating the mass reduction seen in sarcopenia neuronal function characteristic neurodegeneration. Our limited understanding intricate relationships within this hinders accurate diagnosis effective treatment strategies. This review analyzes interrelated mechanisms contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, impaired nutrient delivery. aim is understand common pathways involved suggest comprehensive therapeutic approaches. dysfunctions hinder circulation transportation nutrients, resulting characterized by atrophy weakness. dysfunction have negative physical quality life. Neurodegenerative diseases exhibit comparable pathophysiological affect motor functions. Preventive approaches encompass lifestyle adjustments, addressing integrated therapies improving muscular well-being. Better links can refine strategies yield better patient outcomes. study emphasizes complex interplay between dysfunction, degeneration, decline, highlighting necessity for multidisciplinary Advances domain promise improved diagnostic accuracy, more options, enhanced preventive measures, all contributing higher life elderly population.

Language: Английский

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Role of the transcription factor NRF2 in maintaining the integrity of the Blood-Brain Barrier

Fluids and Barriers of the CNS, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 21, 2024

The Blood-Brain Barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules cells between blood central nervous system. It undergoes structural functional throughout oxidative stress inflammation, which may compromise its integrity contribute to pathogenesis neurodegenerative diseases. Maintaining BBB utmost importance in preventing wide range neurological disorders. NRF2 main transcription factor cellular redox balance inflammation-related gene expression. has also demonstrated potential role regulating tight junction contributing inhibition ECM remodeling, by reducing expression several metalloprotease family members involved maintaining function. Overall, we review current insights on addressing protection against effects dysfunction, discuss involvement maintenance different neuropathological diseases, as well as, some activators have been used vitro vivo animal models for barrier dysfunction. Thus, emerging evidence suggests upregulation target genes could suppress stress, neuroinflammation, restore integrity, increase protection.

Language: Английский

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Brain penetration of peripheral extracellular vesicles from Alzheimer's patients and induction of microglia activation

Journal of Extracellular Biology, Journal Year: 2025, Volume and Issue: 4(1)

Published: Jan. 1, 2025

Alzheimer's disease (AD) is an age-related neurodegenerative pathology. Brain-derived extracellular vesicles (EVs) have been demonstrated to be implicated in AD pathogenesis by facilitating the propagation of Tau, amyloid-β and inflammatory cytokines. However, impact peripheral EVs (pEVs) remains poorly investigated. The objective our study was compare passage pEVs from adults, cognitively healthy elderly, patients through blood-brain barrier (BBB), evaluate their uptake brain assess on microglia activity using vitro vivo models. To this end, were enriched, characterized, fluorescently labelled. endothelial bEnd.3 cells studied a Transwell device with either neuronal or seeded at bottom well. Following internalization patients, adopted amoeboid morphology released heightened level pro-inflammatory cytokine IL-6. further transport across BBB, injected into blood circulation 2-days post-fertilization Tg(flk1:EGFP) zebrafish. biodistribution monitored 1 24 h post-injection confocal microscopy. We that traverse BBB transcytosis subsequently diffuse progressively brain. then internalized radial glial as seen Tg(huc:EGFP) Tg(gfap:EGFP) zebrafish, respectively. Additional experiments performed intrahippocampal injection mouse, indicating spreading throughout cells. These findings contribute novel insights fate following vivo, demonstrate for first time affect activity. This suggests potential mechanism which tissue cues may pathogenesis.

Language: Английский

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Shed Syndecans (1–3), ELA-32, BDNF, NLR, and hs-CRP in Parkinson’s Disease: Appropriate Diagnostic and Prognostic Biomarkers When Combined in a Unique Panel

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4503 - 4503

Published: May 8, 2025

Currently, the management of Parkinson’s disease (PD), second most common neurodegenerative disease, is challenging due to lack consensus on blood biomarkers for diagnostic, prognostic, and outcome purposes. The identification specific sensitive could contribute an early diagnosis and, consequently, facilitate improve prognosis. Several molecules are emerging as potential biomarkers, although current data seem preliminary need further validation. Further, their combination in a panel seems strengthen diagnostic power, allowing them identify PD cases with greater specificity sensitivity. In this study, we evaluated association molecules, including shed syndecans, ELA peptides, CD141, VEGF, BDNF, systemic inflammatory indices, 30 matched healthy controls. Significant differences levels all studied were detected group when compared participants. Univariate multivariate regression analyses, well correlations clinical indicators, severity expressed by Hoehn Yahr (H&Y) scale, highlighted key role independent risk factors. Finally, use receiver operating characteristic (ROC) curves demonstrated value hs-CRP, NLR, syndecans (1–3), ELA-32 PD. Interestingly, performance significantly improved combined panel. Overall, our results suggest that associated likely serve appropriate prognostic especially if

Language: Английский

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β-Amyloids and Immune Responses Associated with Alzheimer’s Disease

Cells, Journal Year: 2024, Volume and Issue: 13(19), P. 1624 - 1624

Published: Sept. 28, 2024

Alzheimer’s disease (AD) is associated with the accumulation of β-amyloids (Aβs) and formation Aβ plaques in brain. Various structural forms isoforms Aβs that have variable propensities for oligomerization toxicity may differentially affect development AD been identified. In addition, there evidence are engaged complex interactions innate adaptive immune systems, both which also play a role regulation onset progression. this review, we discuss what currently known about intricate interplay between response to more in-depth focus on possible roles B cells pathogenesis AD.

Language: Английский

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CD2AP is Co-Expressed with Tropomyosin-Related Kinase A and Ras-Related Protein Rab-5A in Cholinergic Neurons of the Murine Basal Forebrain

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

Published: July 24, 2024

ABSTRACT Basal forebrain cholinergic neurons project to the hippocampus and cortex, are critical for learning memory, central pathogenesis of Alzheimer’s disease (AD). GWAS have consistently shown that genomic variants at CD2AP gene locus associated with significant increased risk AD. studies also genetic in endocytosis genes, including RAB5A , significantly increase susceptibility Previous work our lab has functions as a docking-scaffold/adaptor protein coordinator nerve growth factor (NGF) trophic signaling neurons. We demonstrated positively regulates Rab5-mediated mechanisms primary sensory The purpose this study was perform an vivo characterization expression brain regions most relevant AD investigate colocalization Rab5 murine basal forebrain. Brain tissue perfused, harvested from ChAT BAC -eGFP transgenic mice (N=4 male, N=4 female; aged 10 mo), where (co-) express green fluorescence (GFP) peripheral choline acetyltransferase (ChAT). Frozen sections were used assess specificity reporter mouse along localization both using immunofluorescence (IF) analysis ChAT-GFP+ antibodies against ChAT, Rab5. Image J software develop optimize assay puncta. Experiments repeated follow-up cohort aged-adult (N=2 N=2 18 mo). IF quantified forebrain, diagonal band Broca (vDB), striatal compared results cortical adult brain. Colocalization observed cell bodies striatum, vDB regions, intensity well number positive signal incrementally. analyses revealed near-complete overlap region. conclude healthy brains. These data provide first evidence quantifiable specific (vDB) Together previous research lab, these support role through orchestration retrograde signaling. Ongoing underway verify findings novel model incorporates humanized variant created by MODEL-AD, we aim further how may affect mechanistic components subsequent survival context known amyloid beta Tau pathologies.

Language: Английский

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Vascular Contributions to Healthy Aging and Dementia

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Vascular pathologies are among the most common contributors to neurodegenerative changes across spectrum of normal aging dementia. Cerebral small vessel disease (SVD) encompasses a wide range conditions affecting capillaries, arteries, and arterioles, as well perivascular spaces fluid dynamics in brain, playing significant role vascular contributions cognitive impairment dementia (VCID). These factors can accelerate progression SVD neuronal degeneration. Since is primary risk factor for Alzheimer's (AD) AD-related dementias (ADRD), this Research Topic aims gather recent research better understand healthy age-related impairment. Other include diabetes, lifestyle factors, high cholesterol, inflammation, immune remodeling, all which dysfunction progression. This special issue includes total 21 articles comprising Reviews, Perspectives, Original articles. The cover various technical biological aspects related progress research. We aim promote exchange different fields, including imaging, VCID, molecular biology, neuroinflammation, immunology. Most papers focus on understanding mechanisms AD/ADRD developing new therapeutic strategies.

Language: Английский

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