RESUMO
Parkinson's disease (PD) has two main pathological hallmarks, the loss of nigral dopamine neurons and the proteinaceous aggregations of âº-synuclein (âºSyn) in neuronal Lewy pathology. These two co-existing features suggest a causative association between âºSyn aggregation and the underpinning mechanism of neuronal degeneration in PD. Both increased levels and post-translational modifications of âºSyn can contribute to the formation of pathological aggregations of âºSyn in neurons. Recent studies have shown that the protein is also expressed by multiple types of non-neuronal cells in the brain and peripheral tissues, suggesting additional roles of the protein and potential diversity in non-neuronal pathogenic triggers. It is important to determine (1) the threshold levels triggering âºSyn to convert from a biological to a pathologic form in different brain cells in PD; (2) the dominant form of pathologic âºSyn and the associated post-translational modification of the protein in each cell type involved in PD; and (3) the cell type associated biological processes impacted by pathologic âºSyn in PD. This review integrates these aspects and speculates on potential pathological mechanisms and their impact on neuronal and non-neuronal âºSyn in the brains of patients with PD.