Abstract Details

Title Contribution of the Mitochondrial Complex I Inhibitor Annonacin to the Alpha-synuclein/Tau Co-pathology in Caribbean Atypical Parkinsonism

Topic Movement Disorders

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-010

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.

Authors/Disclosures
Florencia González-Lizárraga PRESENTER	No disclosure on file
Susana Boluda	Susana Boluda has nothing to disclose.
Jose Ruiz Hidalgo	No disclosure on file
Cesar Avila (IMMCA)	No disclosure on file
Sergio Socias (conicet)	No disclosure on file
Luciana Medina	No disclosure on file
Hugo Chaumont (University Hospital Center of Guadeloupe)	No disclosure on file
Emmanuel Roze, MD, PhD	Dr. Roze has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for merz. Dr. Roze has received personal compensation in the range of $500-$4,999 for serving as a Consultant for orkyn. Dr. Roze has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for elivie. Dr. Roze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for allergan. Dr. Roze has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Orkyn. Dr. Roze has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for elivie. Dr. Roze has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aguettant. The institution of Dr. Roze has received research support from merz. The institution of Dr. Roze has received research support from Orkyn. Dr. Roze has received research support from elivie. The institution of Dr. Roze has received research support from allergan. The institution of Dr. Roze has received research support from fondation desmarest. The institution of Dr. Roze has received research support from everpharma. Dr. Roze has received research support from AMADYS. The institution of Dr. Roze has received research support from ADCY5.org. The institution of Dr. Roze has received research support from agence nationale de la recherche. The institution of Dr. Roze has received research support from société française de médecine esthétique. The institution of Dr. Roze has received research support from dystonia medical research foundation.
Rosana Chehin (IMMCA)	No disclosure on file
Rita Vozari (Paris Brain Institute)	No disclosure on file
Patrick-Pierre Michel (Icm)	No disclosure on file
Annie Lannuzel, MD (University Hospital)	Dr. Lannuzel has nothing to disclose.

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