Modeling the cellular fate of alpha-synuclein aggregates: A pathway to pathology

• Published in: Current opinion in neurobiology 2022-02, Vol.72, p.171-177
• Main Authors: Marotta, Nicholas P., Lee, Virginia M-Y.
• Format: Article
• Language: English
• Subjects: alpha-Synuclein - metabolism; Brain - metabolism; Cell Differentiation; Disease Progression; Humans; Parkinson Disease - pathology
• ISSN: 0959-4388; 1873-6882
• DOI: 10.1016/j.conb.2022.01.003

Parkinson's disease is a progressive neurodegenerative disorder that is characterized by pathological protein inclusions that form in the brains of patients, leading to neuron loss and the observed clinical symptoms. These inclusions, containing aggregates of the protein α-Synuclein, spread throughout the brain as the disease progresses. This spreading follows patterns that inform our understanding of the disease. One way to further our understanding of disease progression is to model the discrete steps from when a cell first encounters an aggregate to when those aggregates propagate to new cells. This review will serve to highlight the recent progress made in the effort to better understand the mechanistic steps that determine how this propagation happens at the cellular level. •A central aspect of Parkinson's disease is the cell-to-cell spread of α-Synuclein pathology in the brain.•The spreading of pathology can be modeled by inducing aggregation in cultured cells.•Cellular models allow the isolation of key steps in the pathway from aggregate uptake to propagation.