Astrocytes in physiological aging and Alzheimer's disease (original) (raw)

Chapter 6 Astrocytes ’ Role in Alzheimer ’ s Disease Neurodegeneration

2018

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2010

The circuitry of the human brain is formed by neuronal networks embedded into astroglial syncytia. The astrocytes perform numerous functions, providing for the overall brain homeostasis, assisting in neurogenesis, determining the micro-architecture of the grey matter, and defending the brain through evolutionary conserved astrogliosis programs. Astroglial cells are engaged in neurological diseases by determining the progression and outcome of neuropathological process. Astrocytes are specifically involved in various neurodegenerative diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and various forms of dementia. Recent evidence suggest that early stages of neurodegenerative processes are associated with atrophy of astroglia, which causes disruptions in synaptic connectivity, disbalance in neurotransmitter homeostasis, and neuronal death through increased excitotoxicity. At the later stages, astrocytes become activated and contribute to the neuroinflammatory component of neurodegeneration.

Astroglia dynamics in ageing and Alzheimer's disease

Current opinion in pharmacology, 2015

Ageing of the brain is the major risk factor for neurodegenerative disorders that result in cognitive decline and senile dementia. Ageing astrocytes undergo complex and region specific remodelling which can reflect life-long adaptive plasticity. In neurodegeneration, astroglial cells are similarly a subject for morpho-functional changes hampering the homoeostasis, defence and regeneration of the central nervous system. Region-specific astroglial atrophy with the loss of function and astroglial reactivity have been reported in virtually all forms of neurodegenerative pathologies. Modulating these astroglia changes may represent a fertile ground for novel therapeutic intervention strategies to prevent, delay progression and/or ameliorate pathology. While at present this bodacious goal represents a wishful thinking, further understanding of astroglial role in ageing and neurodegeneration could bring us closer to laying the foundations for such cell-specific therapeutic approaches.

Neurodegeneration and Neuroglia: Emphasis on Astroglia in Alzheimer’s Disease

Pathological Potential of Neuroglia, 2014

Neurodegenerative diseases, which affect almost exclusively humans, are chronic disorders that ultimately result in atrophy of the brain and profound cognitive deficit. Neurodegenerative process reflects a profound failure of brain homeostasis. Neuroglial cells, being primarily the cells responsible for brain homeostasis and defense, naturally contribute to an overall homeostatic failure underlying neurodegeneration. In this chapter we shall deliver a brief on astroglial contribution to common neurodegenerative disorders and then continue with a detailed account on the pathological potential of astroglia in Alzheimer's disease. Astrocytes undergo complex alterations in Alzheimer's disease, which are represented by region-specific atrophy and asthenia at the early stages and reactivity at the late stages of the disease. These complex changes can be considered as pathologically relevant because they may define the early cognitive deficits and the later neurotoxicity in Alzheimer's disease. Targeting astroglia in neurodegeneration may result in new therapeutic strategies aimed at preventing and delaying the progression of Alzheimer's disease.

Astrocytes’ Role in Alzheimer’s Disease Neurodegeneration

Astrocyte - Physiology and Pathology

Central nervous system (CNS) astrocytes are glial cells performing crucial tasks encompassing energy metabolism, neurotransmission, ion and water stable levels, and immune defense and control local blood flow/oxygen levels. Arising from neural stem cells, astrocytes differentiate into subtypes that vary according to animal species. Human cerebral cortex astrocytes are sturdier and cytologically and functionally more complex, control wider domains, and spread calcium signals more quickly than their rodents' counterparts. They actively partake in CNS homeostasis maintenance and functioning by teaming up with their client neurons, other glial cell types, and cerebrovascular cells. Alterations of astrocytes' activities deeply impact on age-related chronic ailments like Alzheimer's disease (AD), the commonest senile dementia; AD involves the growing accumulation of amyloid-β peptides (Aβs) and hyperphosphorylated Tau proteins the astrocytes, and neurons supply following the interaction of their calcium-sensing receptors (CaSRs) with exogenous Aβs. The activated Aβ•CaSR signaling triggers a self-propagating mechanism that spreads the neuropathology among adjacent and far away astrocytes and their neuronal clients causing neurons' death. CaSR antagonists or calcilytics suppress these noxious effects in vitro. Hence, calcilytics are potential therapeutics that could halt the spread of AD neuropathology and safeguard the patients' neuronal viability, cognition, memory, and ultimately life.

The contribution of astrocytes to Alzheimer's disease

Astrocytes were historically classified as supporting cells; however, it is becoming increasingly clear that they actively contribute to neuronal functioning under normal and pathological conditions. As interest in the contribution of neuroinflammation to Alzheimer's disease (AD) progression has grown, manipulating glial cells has become an attractive target for future therapies. Astrocytes have largely been under-represented in studies that assess the role of glia in these processes, despite substantial evidence of astrogliosis in AD. The actual role of astrocytes in AD remains elusive, as they seem to adopt different functions dependent on disease progression and the extent of accompanying parenchymal inflammation. Astrocytes may contribute to the clearance of amyloid β-peptide (Aβ) and restrict the spread of inflammation in the brain. Conversely, they may contribute to neurodegeneration in AD by releasing neurotoxins and neglecting crucial metabolic roles. The present review summarizes current evidence on the multi-faceted functions of astrocytes in AD, highlighting the significant scope available for future therapeutic targets.

The Role of Astrocytes in Astrocytes Alzheimer’s Disease

2020

Astrocytes are highly specialized glial cells and play a crucial role in neuronal functionality and brain functional integrity. Although research on Alzheimer's disease has been concentrated mainly on the role of neurons, increasing evidence comes to light marking the important role of astrocytes in the pathophysiology of Alzheimer's disease. Astrocytes undergo certain morphological changes in Alzheimer's disease and they are thought to participate in Ab metabolism, and to mediate neurotoxicity and neuronal death through Calcium signaling. Here we briefly present the morphological changes of astrocytes and their role in Alzheimer's disease neurodegeneration.

Astroglia in dementia and Alzheimer's disease

Cell Death and Differentiation, 2009

Astrocytes, the most numerous cells in the brain, weave the canvas of the grey matter and act as the main element of the homoeostatic system of the brain. They shape the microarchitecture of the brain, form neuronal-glial-vascular units, regulate the blood-brain barrier, control microenvirionment of the central nervous system and defend nervous system against multitude of insults. Here, we overview the pathological potential of astroglia in various forms of dementias, and hypothesise that both atrophy of astroglia and reactive hypertrophic astrogliosis may develop in parallel during neurodegenerative processes resulting in dementia. We also show that in the transgenic model of Alzheimer's disease, reactive hypertrophic astrocytes surround the neuritic plaques, whereas throughout the brain parenchyma astroglial cells undergo atrophy. Astroglial atrophy may account for early changes in synaptic plasticity and cognitive impairments, which develop before gross neurodegenerative alterations.

The Role of Astrocytes in the Cause of Alzheimer's Disease

Journal of Student Research, 2021

There are three leading hypotheses about the cause of Alzheimer’s Disease (AD): the cholinergic theory, where there is a loss of cholinergic neurons; the amyloid hypothesis, where there is an abnormal buildup of amyloid plaques; and the neurotrophic unbalance hypothesis, which states that AD-related loss of cholinergic signaling and altered amyloid precursor protein (APP) processing are due to alterations in nerve growth factor (NGF). This would ultimately mean that the loss of cholinergic neurons and a buildup of amyloid plaques are due to NGF alterations. Astrocytes are involved in the production of amyloid-beta, inflammation responses, and nerve growth. Therefore, astrocytes are an essential component of all three AD hypotheses. This paper will discuss various known and hypothesized ways that astrocytes affect the symptoms and possible causes of AD.

Astroglial atrophy in Alzheimer’s disease

Pflügers Archiv - European Journal of Physiology, 2019

Astrocytes, a class of morphologically and functionally diverse primary homeostatic neuroglia, are key keepers of neural tissue homeostasis and fundamental contributors to brain defence in pathological contexts. Failure of astroglial support and defence facilitate the evolution of neurological diseases, which often results in aberrant synaptic transmission, neurodegeneration, and death of neurones. disease (AD) astrocytes undergo complex and multifaceted metamorphoses ranging from atrophy with loss of function to reactive astrogliosis with hypertrophy. Astroglial asthenia underlies reduced homeostatic support and neuroprotection that may account for impaired synaptic transmission and neuronal demise. Reactive astrogliosis which mainly develops in astrocytes associated with senile plaque is prominent at the early to moderate stages of AD manifested by mild cognitive impairment; down-regulation of astrogliosis (reflecting astroglial paralysis) is associated with late stages of the disease characterised by severe dementia. Cellspecific therapies aimed at boosting astroglial supportive and defensive capabilities and preventing astroglial paralysis may offer new directions in preventing, arresting or even curing AD-linked neurodegeneration.

Astrocytes in physiological aging and Alzheimer's disease (original) (raw)

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