Astrocytes and the Synucleinopathies

α-Synuclein is an abundantly expressed protein located in the neuronal synapse which accumulates in Lewy body inclusions and synaptic aggregates in neurodegenerative diseases. Although evidence indicates that oligomeric α-synuclein can stimulate neurodegeneration, and α-synuclein amyloid fibrils can spread in a prion-like manner, the initial cause of α-synuclein dysregulation is uncertain. α-Synuclein released from the neuronal presynaptic terminal can accumulate in astrocytes early in disease progression and astrocyte dysfunction has been observed in the same disease phase. Astrocytes provide homeostatic balance to the brain parenchyma through release of neuroprotective factors and clearing of waste products to the vasculature, and astrocytic dysfunction has been shown to cause neuronal cell death. Like protein aggregation in other proteinopathies, such as neurofibrillary tangles and β-amyloid plaques, evidence is emerging that accumulation of abundantly expressed neuronal proteins could be a by-product of initial non-neuronal cellular degeneration. This review examines interactions between α-synuclein and astrocytes with a consideration of an astrocytic cause of synucleinopathy