The Critical Role of Autophagy and Phagocytosis in the Aging Brain DOI Open Access
Stephen C. Bondy,

Meixia Wu

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 57 - 57

Published: Dec. 25, 2024

As the organism ages, there is a decline in effective energy supply, and this retards ability to elaborate new proteins. The consequences of are especially marked gradual brain function. senescence cells their constituent organelles ultimately cause aging entire nervous system. What less immediately obvious that also accompanied by failure catabolic events lead removal non-functional ineffective subcellular components. non-working cellular elements within essential order allow appearance fresh with full range capacities. Thus, maintenance operative mechanisms for dispersal failed tissue components important, its diminished capacity significant contributory factor onset progression age-related neurological disorder. This report discusses underlying autophagy phagocytosis how these can be adversely modulated as proceeds. means which recycling may reinstated aged considered.

Language: Английский

Updates in Alzheimer's disease: from basic research to diagnosis and therapies DOI Creative Commons

Enjie Liu,

Yao Zhang,

Jian–Zhi Wang

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Sept. 4, 2024

Language: Английский

Citations

17
Comprehensive Overview of Alzheimer’s Disease: Etiological Insights and Degradation Strategies DOI Open Access
Manish Kumar Singh,

Yoonhwa Shin,

Songhyun Ju

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6901 - 6901

Published: June 24, 2024

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and affects millions of individuals globally. AD associated with cognitive decline memory loss that worsens aging. A statistical report using U.S. data on estimates approximately 6.9 million suffer from AD, a number projected to surge 13.8 by 2060. Thus, there critical imperative pinpoint address its hallmark tau protein aggregation early prevent manage debilitating effects. Amyloid-β proteins are primarily formation plaques neurofibril tangles in brain. Current research efforts focus degrading amyloid-β or inhibiting their synthesis, particularly targeting APP processing hyperphosphorylation, aiming develop effective clinical interventions. However, navigating this intricate landscape requires ongoing studies trials treatments truly make difference. Genome-wide association (GWASs) across various cohorts identified 40 loci over 300 genes AD. Despite wealth genetic data, much remains be understood about functions these role process, prompting continued investigation. By delving deeper into associations, novel targets such as kinases, proteases, cytokines, degradation pathways, offer new directions for drug discovery therapeutic intervention This review delves biological pathways disrupted identifies how variations within could serve potential treatment strategies. Through comprehensive understanding molecular underpinnings researchers aim pave way more therapies can alleviate burden devastating disease.

Language: Английский

Citations

12
Enhanced BBB penetration and microglia-targeting nanomodulator for the two-pronged modulation of chronically activated microglia-mediated neuroinflammation in Alzheimer’s disease DOI Creative Commons

Ya Wei,

Xue Xia, Xiaorong Wang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) resveratrol co-loaded cationic liposome developed as immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide microglia-targeting (Res@TcMNP/ASO) for management. Res@TcMNP/ASO can enter endothelial cells via D-T7 peptides. Then undergoes acid-responsive cleavage, facilitating escape Res@MNP/ASO from endo/lysosomes cross BBB. detached specifically targets M1-phenotype microglia exposed MG1 peptides prompt simultaneous delivery two drugs into microglia. This not only restore function through ASO but also mitigate stimulation caused reactive oxygen species (ROS) resveratrol, thereby synergistically inhibiting chronic activation alleviate AD. Our results indicate that this combination treatment achieve significant behavioral cognitive improvements late APP/PS1 mice.

Language: Английский

Citations

1
Gut Microbiota Mediates Neuroinflammation in Alzheimer’s Disease: Unraveling Key Factors and Mechanistic Insights DOI
Junyi Liang,

Wang Yueyang,

Bin Liu

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

Language: Английский

Citations

8
Clathrin mediated endocytosis in Alzheimer’s disease: cell type specific involvement in amyloid beta pathology DOI Creative Commons

Sierra Jaye,

Ursula S Sandau,

Julie A. Saugstad

et al.

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: April 17, 2024

This review provides a comprehensive examination of the role clathrin-mediated endocytosis (CME) in Alzheimer's disease (AD) pathogenesis, emphasizing its impact across various cellular contexts beyond neuronal dysfunction. In neurons, dysregulated CME contributes to synaptic dysfunction, amyloid beta (Aβ) processing, and Tau pathology, highlighting involvement early AD pathogenesis. Furthermore, alterations extend non-neuronal cell types, including astrocytes microglia, which play crucial roles Aβ clearance neuroinflammation. Dysregulated these cells underscores broader implications pathophysiology. Despite significant progress, further research is needed elucidate precise mechanisms underlying dysregulation therapeutic implications. Overall, understanding complex interplay between diverse types holds promise for identifying novel targets interventions.

Language: Английский

Citations

5
Synergistic Effects of Olfactory Ecto-Mesenchymal Stem Cell Supernatant and Ellagic Acid on Demyelination and Glial Modulation in a Chronic Multiple Sclerosis Model DOI Creative Commons
Fatemeh Tahmasebi, Elmira Roshani Asl, Faezeh Faghihi

et al.

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

Published: May 2, 2025

Language: Английский

Citations

0
Therapeutic Potential of Fingolimod on Psychological Symptoms and Cognitive Function in Neuropsychiatric and Neurological Disorders DOI

Fatemeh Rahmati‐Dehkordi,

Hadi Khanifar,

Nazanin Najari

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(10), P. 2668 - 2681

Published: June 26, 2024

Language: Английский

Citations

3
Role of Testosterone Signaling in Microglia: A Potential Role for Sex‐Related Differences in Alzheimer's Disease DOI Creative Commons

Haiyan Du,

Akiko Mizokami, Junjun Ni

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Abstract Alzheimer's disease (AD) is less prevalent in men than women, although mechanisms remain unclear. Microglia degrade aggregated amyloid β (Aβ) through the lysosomal system, including autophagy. G protein‐coupled receptor family C group 6 member A (GPRC6A), predominantly expressed mouse microglial MG6 cells, a primary mediator of testosterone signaling. This study examines testosterone's role modulating Aβ‐induced autophagy microglia. Testosterone promotes leading to Aβ clearance cells by suppressing extracellular signal‐regulated kinase (ERK) phosphorylation and subsequently inhibiting mammalian target rapamycin (mTOR) activation, which abrogated shRNA knockdown GPRC6A. In vivo experiments with male 5xFAD AD model mice, activity associated microglia reduced orchiectomy, but restored supplementation. ERK brains mice upregulated orchiectomy. Therefore, involved autophagy‐mediated accumulation human brain samples from patients significantly lower pronounced colocalization p62 aggregates, suggesting enhanced autophagic men. conclusion, enhances microglia, possibly contributing susceptibility

Language: Английский

Citations

0
A mass-producible macaque model displays a durable Alzheimer-like cognitive deficit and hallmark amyloid-β/tau/neurofilament light chain pathologies DOI

Feng He,

Wenjiao Shi,

Wen Liu

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Background Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive deficit and pathological accumulation of amyloid-β (Aβ) tau proteins. The rodent models have contributed greatly to unravel AD pathogenesis, but these been shown a modest clinical translational effectiveness. Objective Therefore, developing mass-producible primate promising for more effective drug development. Methods Here, we constructed monkey simultaneously infusing AAV-Tau Aβ into different brain regions. Results induced monkeys showed durable impairment lasting at least 10 months after modeling. Simultaneously, increased levels total hyperphosphorylated (pTau) several AD-associated sites, neurofilament light chains (NfL) with altered level were detected time points in cerebrospinal fluid and/or plasma using MSD kits. proteins was also positron emission tomography/magnetic resonance imaging immunohistochemical staining. model had significant glial activation; an indicator inflammation commonly seen brains patients. Conclusions Together, this study provides showing AD-like hallmark pathologies (Aβ, tau, NfL, i.e., ATN) deficits. As are genetically metabolically closest humans, will offer discovery development AD.

Language: Английский

Citations

0
Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer’s Disease DOI Open Access
Erin G. Reed-Geaghan, Phaedra R. Keller-Norrell

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17377 - 17377

Published: Dec. 12, 2023

Research into Alzheimer's Disease (AD) describes a link between AD and the resident immune cells of brain, microglia. Further, this suspected is thought to have underlying sex effects, although mechanisms these effects are only just beginning be understood. Many insights result policies put in place by funding agencies such as National Institutes Health (NIH) consider biological variable (SABV) move towards precision medicine due continued lackluster therapeutic options. The purpose review provide an updated assessment current research that summarizes differences pertaining microglia their varied responses AD.

Language: Английский

Citations

8