Work

Mutant and Wild Type Human α-Synucleins Assemble into Elongated Filaments with Distinct Morphologies in Vitro

Year: 1999

Type: article

Abstract: alpha-Synuclein is a soluble presynaptic protein which is pathologically redistributed within intracellular lesions characteristic of several neurodegenerative diseases. Here we demonstrate that wild type and two mutant forms of alpha-synuclein linked to familial Parkinson's disease (Ala30 --> Pro and Ala53 --> Thr) self-aggregate and assemble into 10-19-nm-wide filaments with distinct morphologies under defined in vitro conditions. Immunogold labeling demonstrates that the central region of all these filaments are more robustly labeled than the N-terminal or C-terminal regions, suggesting that the latter regions are buried within the filaments. Since in vitro generated alpha-synuclein filaments resemble the major ultrastructural elements of authentic Lewy bodies that are hallmark lesions of Parkinson's disease, we propose that self-aggregating alpha-synuclein is the major subunit protein of these filamentous lesions.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.274.12.7619

Authors: Benoit I. Giasson, Kunihiro Uryu, John Q. Trojanowski, Virginia M.-Y Lee

Institution: University of Pennsylvania

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430