Parkinsonism genes: culprits and clues
Article first published online: 10 JUL 2006
Journal of Neurochemistry
Volume 99, Issue 4, pages 1062–1072, November 2006
How to Cite
Abeliovich, A. and Flint Beal, M. (2006), Parkinsonism genes: culprits and clues. Journal of Neurochemistry, 99: 1062–1072. doi: 10.1111/j.1471-4159.2006.04102.x
- Issue published online: 8 AUG 2006
- Article first published online: 10 JUL 2006
- Received May 29, 2006; revised manuscript received June 24, 2006; accepted June 27, 2006.
- LRRK2 αSynuclein;
- Parkinson's disease;
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.