| First Author | Lumpkin CJ | Year | 2024 |
| Journal | Mol Brain | Volume | 17 |
| Issue | 1 | Pages | 26 |
| PubMed ID | 38778381 | Mgi Jnum | J:348928 |
| Mgi Id | MGI:7642430 | Doi | 10.1186/s13041-024-01099-1 |
| Citation | Lumpkin CJ, et al. (2024) Broad proteomics analysis of seeding-induced aggregation of alpha-synuclein in M83 neurons reveals remodeling of proteostasis mechanisms that might contribute to Parkinson's disease pathogenesis. Mol Brain 17(1):26 |
| abstractText | Aggregation of misfolded alpha-synuclein (alpha-syn) is a key characteristic feature of Parkinson's disease (PD) and related synucleinopathies. The nature of these aggregates and their contribution to cellular dysfunction is still not clearly elucidated. We employed mass spectrometry-based total and phospho-proteomics to characterize the underlying molecular and biological changes due to alpha-syn aggregation using the M83 mouse primary neuronal model of PD. We identified gross changes in the proteome that coincided with the formation of large Lewy body-like alpha-syn aggregates in these neurons. We used protein-protein interaction (PPI)-based network analysis to identify key protein clusters modulating specific biological pathways that may be dysregulated and identified several mechanisms that regulate protein homeostasis (proteostasis). The observed changes in the proteome may include both homeostatic compensation and dysregulation due to alpha-syn aggregation and a greater understanding of both processes and their role in alpha-syn-related proteostasis may lead to improved therapeutic options for patients with PD and related disorders. |
