⍺-Synuclein levels in Parkinson’s disease – Cell types and forms that contribute to pathogenesis

[Parkinson's disease](https://www.sciencedirect.com/topics/neuroscience/parkinsons-disease "Learn more about Parkinson's disease from ScienceDirect's AI-generated Topic Pages") (PD) has two main pathological hallmarks, the loss of nigral dopamine neurons and the proteinaceous aggregations of ⍺-synuclein (⍺Syn) in neuronal Lewy pathology. These two co-existing features suggest a causative association between ⍺Syn aggregation and the underpinning mechanism of [neuronal degeneration](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/nerve-cell-degeneration "Learn more about neuronal degeneration from ScienceDirect's AI-generated Topic Pages") in PD. Both increased levels and post-translational modifications of ⍺Syn can contribute to the formation of pathological aggregations of ⍺Syn 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 ⍺Syn to convert from a biological to a pathologic form in different brain cells in PD; (2) the dominant form of pathologic ⍺Syn and the associated post-translational modification of the protein in each cell type involved in PD; and (3) the cell type associated [biological processes](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/biological-phenomena-and-functions-concerning-the-entire-organism "Learn more about biological processes from ScienceDirect's AI-generated Topic Pages") impacted by pathologic ⍺Syn in PD. This review integrates these aspects and speculates on potential pathological mechanisms and their impact on neuronal and non-neuronal ⍺Syn in the brains of patients with PD.