Reactive Astrocytes and Alzheimer’s Disease

2021 ◽  
pp. 1-3
Author(s):  
Jamie Talan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reactive Astrocytes

Reactive astrocytes give neurons less support: implications for Alzheimer's disease

2012 ◽  
Vol 33 (2) ◽  
pp. 423.e1-423.e13 ◽  
Author(s):  
Megan L. Steele ◽  
Stephen R. Robinson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reactive Astrocytes

scholarly journals The Many Faces of Astrocytes in Alzheimer's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Michael D. Monterey ◽  
Haichao Wei ◽  
Xizi Wu ◽  
Jia Qian Wu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Research Effort ◽  
Reactive Astrocytes ◽  
Sequencing Technologies ◽  
Recent Developments ◽  
Current Therapies ◽  
Pathological Development ◽  
The Many

Alzheimer's disease (AD) is a progressive neurodegenerative disease and is the most common cause of dementia in an aging population. The majority of research effort has focused on the role of neurons in neurodegeneration and current therapies have limited ability to slow disease progression. Recently more attention has been given to the role of astrocytes in the process of neurodegeneration. Specifically, reactive astrocytes have both advantageous and adverse effects during neurodegeneration. The ability to isolate and depict astrocyte phenotype has been challenging. However, with the recent development of single-cell sequencing technologies researchers are provided with the resource to delineate specific biomarkers associated with reactive astrocytes in AD. In this review, we will focus on the role of astrocytes in normal conditions and the pathological development of AD. We will further review recent developments in the understanding of astrocyte heterogeneity and associated biomarkers. A better understanding of astrocyte contributions and phenotypic changes in AD can ultimately lead to more effective therapeutic targets.

scholarly journals Blocking microglial activation of reactive astrocytes is neuroprotective in models of Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jong-Sung Park ◽  
Tae-In Kam ◽  
Saebom Lee ◽  
Hyejin Park ◽  
Yumin Oh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorders ◽  
Critical Role ◽  
Subcutaneous Administration ◽  
Reactive Astrocytes ◽  
Reactive Astrocyte ◽  
Spatial Learning And Memory ◽  
Neuronal Viability ◽  
Age Related

AbstractAlzheimer’s disease (AD) is the most common cause of age-related dementia. Increasing evidence suggests that neuroinflammation mediated by microglia and astrocytes contributes to disease progression and severity in AD and other neurodegenerative disorders. During AD progression, resident microglia undergo proinflammatory activation, resulting in an increased capacity to convert resting astrocytes to reactive astrocytes. Therefore, microglia are a major therapeutic target for AD and blocking microglia-astrocyte activation could limit neurodegeneration in AD. Here we report that NLY01, an engineered exedin-4, glucagon-like peptide-1 receptor (GLP-1R) agonist, selectively blocks β-amyloid (Aβ)-induced activation of microglia through GLP-1R activation and inhibits the formation of reactive astrocytes as well as preserves neurons in AD models. In two transgenic AD mouse models (5xFAD and 3xTg-AD), repeated subcutaneous administration of NLY01 blocked microglia-mediated reactive astrocyte conversion and preserved neuronal viability, resulting in improved spatial learning and memory. Our study indicates that the GLP-1 pathway plays a critical role in microglia-reactive astrocyte associated neuroinflammation in AD and the effects of NLY01 are primarily mediated through a direct action on Aβ-induced GLP-1R+ microglia, contributing to the inhibition of astrocyte reactivity. These results show that targeting upregulated GLP-1R in microglia is a viable therapy for AD and other neurodegenerative disorders.

scholarly journals Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease

2021 ◽  
Author(s):  
Roland Friedel ◽  
Yong Huang ◽  
Minghui Wang ◽  
Shalaka Wahane ◽  
Mitzy Ríos de Anda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Amyloid Plaque ◽  
Reactive Astrocytes ◽  
Glial Activation ◽  
Plaque Burden ◽  
Aβ Amyloid ◽  
Underlying Mechanisms

Abstract Communication between glial cells has a profound effect on the pathophysiology of Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. Here, we reveal a role of reactive astrocytes in enforcing cell distancing in the glial nets surrounding amyloid plaques, which restricts microglial coverage of Aβ, a prerequisite to detect and engulf amyloid deposits. This process is mediated through guidance receptor Plexin-B1, which we identified as a key network regulator of late-onset AD. We show that Plexin-B1 is robustly upregulated in plaque-associated astrocytes in a corona-like pattern, and its expression levels correlate with plaque burden and disease severity in AD patients. In APP/PS1 mice, an amyloidogenic model of AD, removing Plexin-B1 led to smaller peri-plaque glial nets with relaxed cell distancing and enhanced glial coverage of Aβ plaques, as well as transcriptional changes in both reactive astrocytes and disease-associated microglia that are linked to glial activation and amyloid clearance. Furthermore, amyloid plaque burden was lowered, together with a shift towards dense-core plaques and reduced neuritic dystrophy. Our data thus support a role of Plexin-B1 in controlling glial net structure by imposing cell distancing, leading to poor glial coverage of Aβ, reduced amyloid clearance and compaction. Relaxing cell distancing by targeting guidance receptors may present an alternative strategy to alleviate neuroinflammation in AD by improving glial coverage of Aβ amyloid and plaque compaction.

scholarly journals Fluoro Jade Stains Early and Reactive Astroglia in the Primate Cerebral Cortex

2002 ◽  
Vol 50 (8) ◽  
pp. 1135-1137 ◽  
Author(s):  
Jorge A. Colombo ◽  
Virginia I. Puissant
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Cortex ◽  
Cebus Apella ◽  
Reactive Astrocytes ◽  
Astroglial Cells ◽  
Fluorescent Agent ◽  
Primate Cerebral Cortex

The fluorescent agent Fluoro Jade was applied to cortical brain sections obtained from human patients at early postnatal ages and in patients with Alzheimer's disease, and from a Cebus apella monkey after mechanical lesioning of the cerebral cortex. Fluoro Jade labeled reactive astrocytes and early differentiating astroglial cells.

Reactive astrocytes in Alzheimer’s disease: A double-edged sword

2018 ◽  
Vol 126 ◽  
pp. 44-52 ◽  
Author(s):  
Heejung Chun ◽  
C. Justin Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reactive Astrocytes

nNOS Expression in Reactive Astrocytes Correlates with Increased Cell Death Related DNA Damage in the Hippocampus and Entorhinal Cortex in Alzheimer's Disease

2000 ◽  
Vol 165 (1) ◽  
pp. 12-26 ◽  
Author(s):  
Goran Šimić ◽  
Paul J. Lucassen ◽  
Željka Krsnik ◽  
Božo Krušlin ◽  
Ivica Kostović ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Damage ◽  
Cell Death ◽  
Entorhinal Cortex ◽  
Reactive Astrocytes ◽  
Nnos Expression
Sign in / Sign up

Export Citation Format

Share Document