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Human Molecular Genetics, 1999, Vol. 8, No. 10 1901-1905
© 1999 Oxford University Press

Review

The genetics of disorders withsynuclein pathology and parkinsonism

Matt Farrer, Katrina Gwinn-Hardy, Mike Hutton and John Hardya

Neurogenetics Laboratories, Departments of Pharmacologyand Neurology, Birdsall Building, Mayo Clinic Jacksonville, 4500San Pablo Road, Jacksonville, FL 32224, USA

ABSTRACT

Despite being considered the archetypal non-geneticneurological disorder, genetic analysis of Parkinson’s diseasehas shown that there are at least three genetic loci. Furthermore,these analyses have suggested that the phenotype of the pathogenicloci is wider than simple Parkinson’s disease and may includeLewy body dementia and some forms of essential tremor. Identificationof {alpha}-synuclein as the first of the lociinvolved in Parkinson’s disease and the identificationof this protein in pathological deposits in other disorders hasled to the suggestion that it may share pathogenic mechanisms withmultiple system atrophy, Alzheimer’s disease and priondisease and that these mechanisms are related to a synuclein pathwayto cell death. Finally, genetic analysis of the synuclein diseasesand the tau diseases may indicate that this synuclein pathway isan alternative to the tau pathway to cell death.

FOOTNOTES

a Towhom correspondence should be addressed. Tel: +1 904 9537356; Fax: +1 904 953 7370; Email: hardy.john{at}mayo.edu


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