Astrocyte and Alzheimer’s disease

Cai, Zhiyou; Wan, Chengqun; Liu, Zhou

doi:10.1007/s00415-017-8593-x

Cited by 81 publications

(47 citation statements)

References 77 publications

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“…Also, astrocyte neuroprotective functions may have major therapeutic relevance for AD. In fact, glial cell dysregulation has been suggested as a possible cause of AD [11,24]. In the present study, we demonstrated that sAPPα produced by astrocytes in response to mGlu3R activation could act in a paracrine or autocrine fashion to stimulate Aβ uptake by astrocytes.…”

Section: Discussionsupporting

confidence: 57%

Unraveling the β-amyloid clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor

Durand

Turati

Rudi

et al. 2019

Neurochemistry International

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Discussionsupporting

confidence: 57%

Unraveling the β-amyloid clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor

Durand

Turati

Rudi

et al. 2019

Neurochemistry International

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“…The exercise-induced cognitive improvements in AD mice is often associated with modulation of neuroinflammation [ 7 ]. Glial activation is a well-described feature of the AD brain [ 8 ], manifested as altered cell morphology [ 9 , 10 ] and function [ 11 ]. Both astrocytes and microglia are implicated in AD progression [ 1 ] and recent cell type-specific gene expression data have undoubtedly provided evidence for the strong involvement of astrocytes in human AD [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Astrocyte remodeling in the beneficial effects of long-term voluntary exercise in Alzheimer’s disease

Belaya

Ivanovа

Sorvari

et al. 2020

J Neuroinflammation

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Background Increased physical exercise improves cognitive function and reduces pathology associated with Alzheimer’s disease (AD). However, the mechanisms underlying the beneficial effects of exercise in AD on the level of specific brain cell types remain poorly investigated. The involvement of astrocytes in AD pathology is widely described, but their exact role in exercise-mediated neuroprotection warrant further investigation. Here, we investigated the effect of long-term voluntary physical exercise on the modulation of the astrocyte state. Methods Male 5xFAD mice and their wild-type littermates had free access to a running wheel from 1.5 to 7 months of age. A battery of behavioral tests was used to assess the effects of voluntary exercise on cognition and learning. Neuronal loss, impairment in neurogenesis, beta-amyloid (Aβ) deposition, and inflammation were evaluated using a variety of histological and biochemical measurements. Sophisticated morphological analyses were performed to delineate the specific involvement of astrocytes in exercise-induced neuroprotection in the 5xFAD mice. Results Long-term voluntary physical exercise reversed cognitive impairment in 7-month-old 5xFAD mice without affecting neurogenesis, neuronal loss, Aβ plaque deposition, or microglia activation. Exercise increased glial fibrillary acid protein (GFAP) immunoreactivity and the number of GFAP-positive astrocytes in 5xFAD hippocampi. GFAP-positive astrocytes in hippocampi of the exercised 5xFAD mice displayed increases in the numbers of primary branches and in the soma area. In general, astrocytes distant from Aβ plaques were smaller in size and possessed simplified processes in comparison to plaque-associated GFAP-positive astrocytes. Morphological alterations of GFAP-positive astrocytes occurred concomitantly with increased astrocytic brain-derived neurotrophic factor (BDNF) and restoration of postsynaptic protein PSD-95. Conclusions Voluntary physical exercise modulates the reactive astrocyte state, which could be linked via astrocytic BDNF and PSD-95 to improved cognition in 5xFAD hippocampi. The molecular pathways involved in this modulation could potentially be targeted for benefit against AD.

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“…Accumulating evidence demonstrates that impairment in astrocyte reaction to external injury can trigger or exacerbate hyperphosphorylation of tau as well as Aβ pathologies, leading to neuronal dysfunction. 88 Despite independent roles in neuroinflammation, there is growing evidence for intense interactions between microglia and astrocytes in AD. 89 First, microglia-secreted cytokines can activate astrocytes, which leads to loss of physiological functions and become neuronal toxicity.…”

Section: Neuroinflammationmentioning

confidence: 99%

Harnessing endophenotypes and network medicine for Alzheimer's drug repurposing

Fang

Pieper

Nussinov

et al. 2020

Medicinal Research Reviews

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Following two decades of more than 400 clinical trials centered on the "one drug, one target, one disease" paradigm, there is still no effective disease-modifying therapy for Alzheimer's disease (AD). The inherent complexity of AD may challenge this reductionist strategy. Recent observations and advances in network medicine further indicate that AD likely shares common underlying mechanisms and intermediate pathophenotypes, or endophenotypes, with other diseases. In this review, we consider AD pathobiology, disease comorbidity, pleiotropy, and therapeutic development, and construct relevant endophenotype networks to guide future therapeutic development. Specifically, we discuss six main endophenotype hypotheses in AD: amyloidosis, tauopathy, neuroinflammation, mitochondrial dysfunction, vascular dysfunction, and lysosomal dysfunction. We further consider how

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Astrocyte and Alzheimer’s disease

Cited by 81 publications

References 77 publications

Unraveling the β-amyloid clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor

Unraveling the β-amyloid clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor

Astrocyte remodeling in the beneficial effects of long-term voluntary exercise in Alzheimer’s disease

Harnessing endophenotypes and network medicine for Alzheimer's drug repurposing

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