Contribution of the Mitochondrial Complex I Inhibitor Annonacin to the Alpha-synuclein/Tau Co-pathology in Caribbean Atypical Parkinsonism
Florencia González-Lizárraga1, Susana Boluda3, José Ruis Hidalgo4, Cesar Avila2, Benjamin Socias2, Luciana Medina 1, Hugo Chaumont5, Emmanuel Roze6, Rosana Chehin1, Rita Raisman-Vozari6, Patrick-Pierre Michel6, Annie Lannuzel5
1IMMCA, 2CONICET-UNT-SIPROSA, IMMCA, 3Paris Brain Institute-ICM, 4UNT-FBQF-Argentina, 5University Hospital of Guadeloupe, 6ICM
Objective:
To further characterize protein amyloid aggregation atypical degenerative parkinsonism in the French Caribbean islands, and to determine to what extent annonacin could contribute to this pathogenic process.
Background:
High consumption of Annonacae plant products containing the mitochondrial toxin annonacin has been previously recognized as a risk factor for Caribbean atypical parkinsonism.
Design/Methods:
We performed post-mortem histopathological analysis of brain samples from 7 patients, and more specifically assessed the distribution and burden of alpha-Synuclein (αS) and tau lesions. We also studied the impact of annonacin on αS and tau aggregation using Thioflavin-T (ThT) fluorescent assays with corresponding recombinant human proteins as substrate.
Results:
Caribbean atypical parkinsonism represents a group of patients with heterogeneous clinical and histopathogical features. A tau/αS co-pathology, with a predominance of either αS or tau lesions, is observed in the majority (5/7) of cases. Annonacin amplifies αS aggregation, and leads to the formation of new fibrillary species having the capacity to seed tau aggregation.
Conclusions:
We suggest that annonacin may contribute to degenerative Caribbean parkinsonism by modulating the production of tau and αS pathogenic protein assemblies.