Neurobiology
The Effect of Fragmented Pathogenic α-Synuclein Seeds on Prion-like Propagation
Aggregates of abnormal proteins are widely observed in neuronal and glial cells of patients with various neurodegenerative diseases, and it has been proposed that prion-like behavior of these proteins can account for not only the onset but also the progression of these diseases. However, it is not yet clear which abnormal protein structures function most efficiently as seeds for prion-like propagation. In this study, we aimed to identify the most pathogenic species of α-synuclein (α-syn), the main component of the Lewy bodies and Lewy neurites that are observed in α-synucleinopathies.Templated Aggregation of TAR DNA-binding Protein of 43 kDa (TDP-43) by Seeding with TDP-43 Peptide Fibrils
TAR DNA-binding protein of 43 kDa (TDP-43) has been identified as the major component of ubiquitin-positive neuronal and glial inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Aggregation of TDP-43 to amyloid-like fibrils and spreading of the aggregates are suggested to account for the pathogenesis and progression of these diseases. To investigate the molecular mechanisms of TDP-43 aggregation, we attempted to identify the amino acid sequence required for the aggregation.
