Glia in the pathogenesis of neurodegenerative diseases (original) (raw)
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Astroglia are the homoeostatic cells of the central nervous system, which participate in all essential functions of the brain. Astrocytes support neuronal networks by handling water and ion fluxes, transmitter clearance, provision of antioxidants, and metabolic precursors and growth factors. The critical dependence of neurons on constant support from the astrocytes confers astrocytes with intrinsic neuroprotective properties. On the other hand, loss of astrocytic support or their pathological transformation compromises neuronal functionality and viability. Manipulating neuroprotective functions of astrocytes is thus an important strategy to enhance neuronal survival and improve outcomes in disease states.
The role of astroglia in neuroprotection
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Astrocytes are the main neural cell type responsible for the maintenance of brain homeostasis. They form highly organized anatomical domains that are interconnected into extensive networks. These features, along with the expression of a wide array of receptors, transporters, and ion channels, ideally position them to sense and dynamically modulate neuronal activity. Astrocytes cooperate with neurons on several levels, including neurotransmitter trafficking and recycling, ion homeostasis, energy metabolism, and defense against oxidative stress. The critical dependence of neurons upon their constant support confers astrocytes with intrinsic neuroprotective properties which are discussed here. Conversely, pathogenic stimuli may disturb astrocytic function, thus compromising neuronal functionality and viability. Using neuroinflammation, Alzheimer's disease, and hepatic encephalopathy as examples, we discuss how astrocytic defense mechanisms may be overwhelmed in pathological conditi...
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The common denominator of neurodegenerative diseases, which mainly affect humans, is the progressive death of neural cells resulting in neurological and cognitive deficits. Astroglial cells are the central elements of the homoeostasis, defence and regeneration of the central nervous system, and their malfunction or reactivity contribute to the pathophysiology of neurodegenerative diseases. Pathological remodelling of astroglia in neurodegenerative context is multifaceted. Both astroglial atrophy with a loss of function and astroglial reactivity have been identified in virtually all the forms of neurodegenerative disorders. Astroglia may represent a novel target for therapeutic strategies aimed at preventing and possibly curing neurodegenerative diseases.
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.
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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.
Astroglia in neurological diseases
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Astroglia encompass a subset of versatile glial cells that fulfill a major homeostatic role in the mammalian brain. Since any brain disease results from failure in brain homeostasis, astroglial cells are involved in many, if not all, aspects of neurological and/or psychiatric disorders. In this article, the roles of astrocytes as homeostatic cells in healthy and diseased brains are surveyed. These cells can mount the defence response to the insult of the brain, astrogliosis, when and where they display hypertrophy. Interestingly, astrocytes can alternatively display atrophy in some pathological conditions. Various pathologies, including Alexander and Alzheimer's diseases, amyotrophic lateral sclerosis, stroke and epilepsy, to mention a few, are discussed. Astrocytes could represent a novel target for medical intervention in the treatment of brain disorders.
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Astrocytes are the most explored non-neuronal cells in the brain under neurophysiological and neurodegenerative conditions. Extensive research has been done to understand their specific role during neuropathological conditions but still the existing findings could not conclude their mechanism of action and their specific role in neurodegenerative conditions. This review discusses their physiological and pathological roles, their activation, morphological alterations and their probable use in search of new therapeutic targets for the treatment of neurodegenerative diseases.
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Astrocytes are a major constituent of the central nervous system. These glia play a major role in regulating blood-brain barrier function, the formation and maintenance of synapses, glutamate uptake, and trophic support for surrounding neurons and glia. Therefore, maintaining the proper functioning of these cells is crucial to survival. Astrocyte defects are associated with a wide variety of neuropathological insults, ranging from neurodegenerative diseases to gliomas. Additionally, injury to the CNS causes drastic changes to astrocytes, often leading to a phenomenon known as reactive astrogliosis. This process is important for protecting the surrounding healthy tissue from the spread of injury, while it also inhibits axonal regeneration and plasticity. Here, we discuss the important roles of astrocytes after injury and in disease, as well as potential therapeutic approaches to restore proper astrocyte functioning.