Astrocytes in Neurodegenerative Diseases: A Perspective from Tauopathy and α-Synucleinopathy

Neurodegenerative diseases are aging-associated chronic pathological conditions affecting primarily neurons in humans. Inclusion bodies containing misfolded proteins have emerged as a common pathologic feature for these diseases. In many cases, misfolded proteins produced by a neuron can be transmitted to another neuron or a non-neuronal cell, leading to the propagation of disease-associated pathology. While undergoing intercellular transmission, misfolded proteins released from donor cells can often change the physiological state of recipient cells. Accumulating evidence suggests that astrocytes are highly sensitive to neuron-originated proteotoxic insults, which convert them into an active inflammatory state. Conversely, activated astrocytes can release a plethora of factors to impact neuronal functions. This review summarizes our current understanding of the complex molecular interplays between astrocyte and neuron, emphasizing on Tau and α-synuclein (α-syn), the disease-driving proteins for Alzheimer's and Parkinson's diseases, respectively.