The Role of Glia in Alpha-Synucleinopathies

alpha-Synuclein (AS)-positive inclusions are the pathological hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), all belonging to the category of alpha-synucleinopathies. alpha-Synucleinopathies represent progressive neurodegenerative disorders characterised by increasing incidences in the population over the age of 65. The relevance of glial reactivity and dysfunction in alpha-synucleinopathies is highlighted by numerous experimental evidences. Glial AS inclusion pathology is prominent in oligodendroglia of MSA (glial cytoplasmic inclusions) and is a common finding in astroglial cells of PD and DLB, resulting in specific dysfunctional responses. Involvement of AS-dependent astroglial and microglial activation in neurodegenerative mechanisms, and therefore in disease initiation and progression, has been suggested. The aim of this review is to summarise and discuss the multifaceted responses of glial cells in alpha-synucleinopathies. The beneficial, as well as detrimental, effects of glial cells on neuronal viability are taken into consideration to draw an integrated picture of glial roles in alpha-synucleinopathies. Furthermore, an overview on therapeutic approaches outlines the difficulties of translating promising experimental studies into successful clinical trials targeting candidate glial pathomechanisms.