Dysfunctional glia: contributors to neurodegenerative disorders

Abstract

Astrocytes are integral components of the central nervous system, where they are involved in numerous functions critical for neuronal development and functioning, including maintenance of blood-brain barrier, formation of synapses, supporting neurons with nutrients and trophic factors, and protecting them from injury. These roles are markedly affected in the course of chronic neurodegenerative disorders, often before the onset of the disease. In this review, we summarize the recent findings supporting the hypothesis that astrocytes play a fundamental role in the processes contributing to neurodegeneration. We focus on α-synucleinopathies and tauopathies as the most common neurodegenerative diseases. The mechanisms implicated in the development and progression of these disorders appear not to be exclusively neuronal, but are often related to the astrocytic-neuronal integrity and the response of astrocytes to the altered microglial function. A profound understanding of the multifaceted functions of astrocytes and identification of their communication pathways with neurons and microglia in health and in the disease is of critical significance for the development of novel mechanism-based therapies against neurodegenerative disorders.

Keywords

• astrocytes; microglia; neurodegeneration; neuroinflammation; synaptic dysfunction; synucleinopathies; tauopathies