Parkinsonism genes: culprits and clues

Authors

  • Asa Abeliovich,

    1. Departments of Pathology and Neurology, Center for Neurobiology and Behavior, and Taub Institute, Columbia University, College of Physicians and Surgeons 15–403, 630 W 168th. St., New York, NY 10032 USA
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  • M. Flint Beal

    1. Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA
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Address correspondence and reprint requests to Asa Abeliovich, Departments of Pathology and Neurology, Center for Neurobiology and Behavior, and Taub Institute, Columbia University, College of Physicians and Surgeons 15–403, 630 W 168th. St., New York, NY 10032 USA. Email: aa900@columbia.edu

Abstract

Parkinson's disease (PD) is characterized by a unique clinical constellation that includes: slowness, rigidity, gait difficulty, and tremor at rest. Pathological studies have linked this presentation to the loss of midbrain dopamine neurons (Gelb et al. 1999) although other neuronal populations are also targeted in PD. Epidemiological data implicate both genetic and environmental factors in the etiology of the disease. The identification of a series of genes that underlie relatively rare, familial forms of Parkinsonism (a clinical term that encompasses ‘sporadic’ PD, familial Parkinson's-like forms, as well as other related syndromes) has brought excitement to the field. Three of the mutated familial Parkinsonism (FP) genes: Parkin, DJ-1, and PINK1, typically present with apparent autosomal recessive inheritance and are implicated in mitochondria and oxidative stress-related survival pathways. Two other FP genes: α-Synuclein (αSyn) and LRRK2, present in an autosomal dominant pattern and are associated with prominent intracellular protein inclusions. A series of recent publications suggest novel pathways that may link the FP genes.

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