Chapter 6 Astrocytes ’ Role in Alzheimer ’ s Disease Neurodegeneration (original) (raw)
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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.
Astrocytes in Alzheimer's disease
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.
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.
Astrocytes in physiological aging and Alzheimer's disease
Neuroscience, 2015
Astrocytes are fundamental for homoeostasis, defence and regeneration of the central nervous system. Loss of astroglial function and astroglial reactivity contributes to the aging of the brain and to neurodegenerative diseases. Changes in astroglia in aging and neurodegeneration are highly heterogeneous and region-specific. In animal models of Alzheimer's disease (AD) astrocytes undergo degeneration and atrophy at the early stages of pathological progression, which possibly may alter the homeostatic reserve of the brain and contribute to early cognitive deficits. At later stages of AD reactive astrocytes are associated with neurite plaques, the feature commonly found in animal models and in human diseased tissue. In animal models of the AD reactive astrogliosis develops in some (e.g. in the hippocampus) but not in all regions of the brain. For instance, in entorhinal and prefrontal cortices astrocytes do not mount gliotic response to emerging β-amyloid deposits. These deficits i...
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.
Review Free Access The role of astrocytes in Alzheimer's disease, A systematic review
Introduction: Alzheimer's disease (AD), the most common neurodegenerative disease in the world, appears in two forms, early and late. Pathologically, an amyloid beta peptide is the hallmark of this disease which is followed by synaptic dysfunction, brain atrophy, and accumulation of neuronal tangles. The purpose of this study is to review the researchers on astrocytes' role in the progress of AD. Materials and Methods: A comprehensive search was conducted in databases articles focusing on key terms "Inflammatory reactions", "Alzheimer's disease", "Inflammatory factors" and "Astrocytes" and Boolean operators. Articles before 2001 were removed. Results: Finally, after analyzing the selected articles, 20 articles were extracted and included in this review. Conclusion: Astrocytes are a group of glial cells in the central nervous system. The inflammatory activity of astrocytes plays a role in the development and progression of Alzheimer's disease. They strengthen the function of synapses by secreting neurotrophic factors. They also clear amyloid beta peptides from nerve tissue. Amyloid beta peptides bind to specific receptors on these cells and change the activity of these cells from anti-inflammatory to inflammatory type. It seems that astrocytes play a pivotal role in the development and progression of AD, particularly at the late stage of the disease. Finding a rational strategy to suppress inflammatory A1 phenotype might be a promising tool to slow down the progress of AD.
International Journal of Molecular Sciences
This work aimed at assessing Alzheimer’s disease (AD) pathogenesis through the investigation of the astrocytic role to transduce the load of amyloid-beta (Aβ) into neuronal death. The backbone of this review is focused on the deepening of the molecular pathways eliciting the activation of astrocytes crucial phenomena in the understanding of AD as an autoimmune pathology. The complex relations among astrocytes, Aβ and tau, together with the role played by the tripartite synapsis are discussed. A review of studies published from 1979 to 2023 on Scopus, PubMed and Google Scholar databases was conducted. The selected papers focused not only on the morphological and metabolic characteristics of astrocytes, but also on the latest notions about their multifunctional involvement in AD pathogenesis. Astrocytes participate in crucial pathways, including pruning and sprouting, by which the AD neurodegeneration evolves from an aggregopathy to neuroinflammation, loss of synapses and neuronal dea...
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.
Astrocytes and Inflammatory Processes in Alzheimer’s Disease
IntechOpen eBooks, 2020
A significant increase in inflammation has been shown to be a crucial factor in the progression of the Alzheimer's disease (AD). Moreover, inflammatory signals are already present in mild cognitive impairment (MCI) patients before they develop AD. The amyloid hypothesis argues that in AD, there is an increase in oxidative stress caused by the accumulation of β-amyloid (Aβ) and that its elimination should be a priority. Also, hyperphosphorylation of the protein TAU occurs, which is characteristic of this disease. In AD oxidative stress processes occur and also inflammation. The basal chronic inflammation produces a cascade of cellular, such as astrocytes and microglial cells, and molecular processes in AD patients. We here have tried to explore the action of the inflammatory process and its implication in the neurodegenerative process of the AD. We can see that the role of Aβ is only one component that gives rise to inflammation, probably mediated by activation of microglia and astrocytes with the goal of getting rid of these brain waste products. In fact, it is related to a greater degree with the progression of the disease and worsening of the symptoms with the increase of phosphorylated TAU in different parts of the brain.