The Chaperone-Like Activity of α-Synuclein Attenuates Aggregation of Its Alternatively Spliced Isoform, 112-Synuclein In Vitro: Plausible Cross-Talk between Isoforms in Protein Aggregation

摘要: Abnormal oligomerization and aggregation of α-synuclein (α-syn/WT-syn) has been shown to be a precipitating factor in the pathophysiology Parkinson's disease (PD). Earlier observations on induced-alternative splicing α-syn by Parkinsonism mimetics as well identification region specific abnormalities transcript levels 112-synclein (112-syn) diseased subjects underscores role 112-syn PD. In present study, we sought identify potential presence or absence WT-syn predict its plausible protein events. Results demonstrate that unlike WT-syn, lack 28 aa C-terminus results loss chaperone-like activity with concomitant gain vulnerability heat-induced time-dependent fibrillation. The effects were dose significant was evident at low 45°C following 10 min incubation. aggregates found ill-defined structures weakly positive towards Thioflavin-T (ThT) staining compared clearly distinguishable ThT extended fibrils resulting upon 24 h incubation 37°C. Further, significantly attenuated manner. On contrary, synergistically enhanced fibrillation 112-syn. Overall, findings highlight cross-talk between isoforms relative abundance these may dictate nature fate aggregates.