miR-34a/TAN1/CREB Axis Engages in Alleviating Oligodendrocyte Trophic Factor-Induced Myelin Repair Function and Astrocyte-Dependent Neuroinflammation in the Early Stages of Alzheimer's Disease: The Anti-Neurodegenerative Effect of Treadmill Exercise

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(4), P. 1105 - 1120

Published: Jan. 30, 2024

Language: Английский

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Astrocyte and oligodendrocyte pathology in Alzheimer's disease

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00540 - e00540

Published: Feb. 1, 2025

Astrocytes and oligodendrocytes, once considered passive support cells, are now recognized as active participants in the pathogenesis of Alzheimer's disease. Emerging evidence highlights critical role that these glial cells play pathological features Alzheimer's, including neuroinflammation, excitotoxicity, synaptic dysfunction, myelin degeneration, which contribute to neurodegeneration cognitive decline. Here, we review current understanding astrocyte oligodendrocyte pathology disease highlight research supports therapeutic potential modulating functions treat

Language: Английский

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Revealing cell vulnerability in Alzheimer’s disease by single-cell transcriptomics

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 139, P. 73 - 83

Published: May 24, 2022

Alzheimer's disease (AD) is a neurodegenerative disorder that by affecting specific brain cell types and regions cause severe pathological functional changes in memory neural circuits. A comprehensive knowledge of the pathogenic mechanisms underlying AD requires deeper understanding cell-specific responses through integrative molecular analyses. Recent application high-throughput single-cell transcriptomics to postmortem tissue has proved powerful unravel susceptibility biological networks responding amyloid tau pathologies. Here, we review transcriptomic studies successfully applied decipher gene expression programs pathways patients. Transcriptional information reveals both common signatures major cerebral types, including astrocytes, endothelial cells, microglia, neurons, oligodendrocytes. Cell type-specific transcriptomes associated with pathology clinical symptoms are related affecting, among others pathways, synaptic function, inflammation, proteostasis, death, oxidative stress, myelination. The general picture emerges from systems-level spatiotemporal pattern diversity novel subpopulations affected brain. We argue broader implementation larger human cohorts using standardized protocols fundamental for reliable assessment temporal regional cell-type profiling. possibility applying this methodology personalized medicine clinics still challenging but opens new roads future diagnosis treatment dementia.

Language: Английский

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Astrocytic APOE4 removal confers cerebrovascular protection despite increased cerebral amyloid angiopathy

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: March 16, 2023

Abstract Background Alzheimer Disease (AD) and cerebral amyloid angiopathy (CAA) are both characterized by amyloid-β (Aβ) accumulation in the brain, although Aβ deposits mostly brain parenchyma AD cerebrovasculature CAA. The presence of CAA can exacerbate clinical outcomes patients promoting spontaneous intracerebral hemorrhage ischemia leading to CAA-associated cognitive decline. Genetically, share ε4 allele apolipoprotein E ( APOE ) gene as strongest genetic risk factor. Although tremendous efforts have focused on uncovering role APOE4 parenchymal plaque pathogenesis AD, mechanistic studies investigating still lacking. Here, we addressed whether abolishing generated astrocytes, major producers APOE, is sufficient ameliorate vessel damage. Methods We transgenic mice that deposited plaques which expression be selectively suppressed astrocytes. At 2-months-of-age, a timepoint preceding formation, was removed from astrocytes 5XFAD knock-in mice. Mice were assessed at 10-months-of-age for pathology, gliosis, vascular integrity. Results Reducing levels shifted deposition fibrillar cerebrovasculature. However, despite increased CAA, astrocytic removal reduced overall Aβ-mediated gliosis also led cerebrovascular integrity function vessels containing Conclusion In mouse model reduction derived specifically vasculature, reduce dysfunction.

Language: Английский

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The role of glial autophagy in Alzheimer’s disease

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(11), P. 4528 - 4539

Published: Sept. 7, 2023

Language: Английский

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