Astrocytes: inexplicable cells in neurodegeneration (original) (raw)
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Journal of Pharmaceutical Research International, 2021
At present, research in the field of the brain does not cease to surprise us with new facts and discoveries that no one could have suspected about 30 years ago. But it was at the time when it became clear that the cerebral neurons are not the only cells that can respond to changes in the external environment. A real scientific boom began to study a heterogeneous group called glia. And scientists are paying close attention to the largest of them – astrocytes. Understanding the importance of astrocytes in the mechanisms of repair and damage to brain cells in various forms of CNS pathology determines the possibility of targeted search for drugs that affect the rate of development of reactive astrogliosis in response to various brain injuries. At the same time, pharmacological modulation of activated astrocytes and other components of glia can be an integral part of the therapy of neurological diseases.
Role of astrocytes in major neurological disorders: The evidence and implications
IUBMB Life, 2013
Given the huge amount and great complexity of astrocyte functions in the maintenance of brain homeostasis, it is easily understood how alterations in their physiology may be involved in the pathogenesis of many, if not all, neurological disorders. This assumption is strongly supported by accumulated evidence produced in humans and in experimental models of pathology. Based on these considerations, it is reasonable to encourage studies aimed at improving the knowledge about the implicated mechanisms, and astroglial cells can be considered as the innovative target for new, and possibly more effective, drug therapies.
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 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.
International Journal of Molecular Sciences
Alzheimer’s disease (AD) is a frequent and disabling neurodegenerative disorder, in which astrocytes participate in several pathophysiological processes including neuroinflammation, excitotoxicity, oxidative stress and lipid metabolism (along with a critical role in apolipoprotein E function). Current evidence shows that astrocytes have both neuroprotective and neurotoxic effects depending on the disease stage and microenvironmental factors. Furthermore, astrocytes appear to be affected by the presence of amyloid-beta (Aβ), with alterations in calcium levels, gliotransmission and proinflammatory activity via RAGE-NF-κB pathway. In addition, astrocytes play an important role in the metabolism of tau and clearance of Aβ through the glymphatic system. In this review, we will discuss novel pharmacological and non-pharmacological treatments focused on astrocytes as therapeutic targets for AD. These interventions include effects on anti-inflammatory/antioxidant systems, glutamate activity...
Chapter 6 Astrocytes ’ Role in Alzheimer ’ s Disease Neurodegeneration
2018
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 o...
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.