PARKIN as a pathogenic gene for autosomal recessive juvenile parkinsonism
Parkinson’s disease is a common neurodegenerative disease with complex clinical features. Recently, we idenfied a novel gene named Parkin to be responsible for the pathogenesis of autosomal recessive juvenile parkinsonism (AR-JP). Various mutations were found in AR-JP patients of Japanese and other ethnic origins, providing a definitive evidence for the Parkin to be a causative gene for AR-JP. The predicted structure of Parkin protein and its mutation provide important clues for studying the functional role of the Parkin protein in leading to selective degeneration of nigral neurons in the brains of AR-JP patients.
KeywordsLewy Body Nigral Neuron Parkin Gene Juvenile Parkinsonism Autosomal Recessive Juvenile Parkin
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- Hattori N, Kitada T, Matsumine H, Asakawa S, Yamamura Y, Yoshino H, Kobayashi T, Yokochi M, Wang M, Yoritaka A, Kondo T, Kuzuhara S, Nakamura S, Shimizu N, Mizuno Y (1998) Molecular genetic analysis of a novel Parkin gene in Japanese families with AR-JP: evidence for variable homozygous deletions in the parkin gene in affected individuals. Ann Neurol 44: 935–941PubMedCrossRefGoogle Scholar
- Matsumine H, Saito M, Shimoda-Matsubayashi S, Tanaka H, Ishikawa A, Nakagawa-Hattori Y, Yokochi M, Kobayashi T, Igarashi S, Takano H, Sanpei K, Koike R, Mori H, Kondo T, Mizutani Y, Schaffer A.A., Yamamura Y, Nakamura S, Kuzuhara S, Tsuji S, Mizuno Y (1997) Localization of a gene for autosomal rcessive form of juvenile parkinsonism (AR-JP) to chromosome 6q25.2-27. Am J Hum Genet 60:588–596PubMedGoogle Scholar
- Parkinson J (1817) An essay on the shaking palsy. Whittingham and Rowland, LondonGoogle Scholar
- Polymeropoulos M.H., Lavedan C, Laroy E, Ide S.E., Dehejia A, Pike A.D.B., Root H, Rubenstein J, Boyer R, Stenroos E.S., Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson W.G., Lazzarini A.M., Duvoisin R.C., Di Irio G, Globe L.I., Nussbaum R.L. (1997) Mutations in the a-synuclein gene identified in families with Parkinson’s disease. Science 276: 2045–2047PubMedCrossRefGoogle Scholar
- Riess O, Jakes R, Kruger R (1998) Genetic dissection of familial Parkinson’s disease. Mol Med Today October: 438–444Google Scholar
- Shimizu N (1999) Human genome project: current status, Keio strategy, and prospects. In: Uyemura K, Kawamura K, Yazaki T (eds) Keio University Symposium for Life Science and Medicine, vol 2. Neural development. Springer, Berlin Heidelberg New York Tokyo, pp 535–540Google Scholar
- Shimura H, Hattori N, Kubo S, Yoshikawa M, Kitada T, Matsumine H, Asakawa S, Minoshima S, Yamamura Y, Shimizu N, Mizuno Y (1999) Immunohistochemical and subcellular localization of parkin protein: absence of protein in autosomal recessive juvenile parkinsonism patients. Ann Neurol 45: 668–672PubMedCrossRefGoogle Scholar
- Yamamura Y, Arihiro K, Hohriyama T, Nakamura S (1993) Early-onset parkinsonism with diurnal fluctuation-clinical and pathological studies. Clin Neurol (Tokyo) 33:491–496Google Scholar