The ubiquitin pathway in Parkinson's disease

• Published in: Nature (London) Vol. 395; no. 6701; pp. 451 - 452
• Main Authors: Leroy, Elisabeth, Boyer, Rebecca, Auburger, Georg, Leube, Barbara, Ulm, Gudrun, Mezey, Eva, Harta, Gyongyi, Brownstein, Michael J, Jonnalagada, Sobhanadditya, Chernova, Tanya, Dehejia, Anindya, Lavedan, Christian, Gasser, Thomas, Steinbach, Peter J, Wilkinson, Keith D, Polymeropoulos, Mihael H
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-10-1998
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Brain - enzymology; Catalysis; DNA; Escherichia coli; Female; Humans; Male; Mice; Middle Aged; Molecular Sequence Data; Mutation; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson's disease; Point Mutation; Rats; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Thiolester Hydrolases - genetics; Thiolester Hydrolases - metabolism; Ubiquitin Thiolesterase; Ubiquitins - metabolism
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/26652

Mutations of the α-synuclein gene, have been identified in some familial forms of Parkinson's disease, and α-synuclein protein has been shown to accumulate in the brains of patients with the disease. These findings suggest that Parkinson's disease may be caused by the abnormal aggregation of α-synuclein protein. Here we have identified in a German family with Parkinson's disease a missense mutation in the ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene. We show that this mutation, Ile93Met, causes a partial loss of the catalytic activity of this thiol protease, which could lead to aberrations in the proteolytic pathway and aggregation of proteins.