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Induction of de novo α-synuclein fibrillization in a neuronal model for Parkinson's disease

Fares, Mohamed-Bilal, Maco, Bohumil, Oueslati, Abid, Rockenstein, Edward, Ninkina, Natalia, Buchman, Vladimir L., Masliah, Eliezer and Lashuel, Hilal A. 2016. Induction of de novo α-synuclein fibrillization in a neuronal model for Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 113 (7) , E912-E921. 10.1073/pnas.1512876113

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Abstract

Although it has been established for over 100 years that Lewy bodies (LBs) represent the major pathological hallmark of Parkinson's disease (PD), we still do not know why these fibrillar intraneuronal inclusions of α-synuclein (α-Syn) protein form, or how they contribute to disease progression. One of the major causes underlying this gap in knowledge is the lack of animal models that reproduce the formation of fibrillar LB-like inclusions. In this study, we show that the absence of human α-Syn (hα-Syn) fibrillization into LBs in mice can be attributed to interactions between hα-Syn and its endogenously expressed mouse α-Syn homologue. Moreover, we provide well-characterized primary neuronal and in vivo models that recapitulate the main molecular feature of PD, bona fide α-Syn fibrillization.

Item Type: Article
Status: Published
Schools: Biosciences
Subjects: Q Science > QR Microbiology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: National Academy of Sciences
ISSN: 0027-8424
Date of First Compliant Deposit: 7 April 2016
Date of Acceptance: 4 January 2016
Last Modified: 03 Nov 2017 05:47
URI: http://orca.cf.ac.uk/id/eprint/88673

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