Parkinsonism genes: culprits and clues.
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: alpha-Synuclein (alphaSyn) 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.
Abeliovich
Asa
A
Department of Pathology, Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons 15-403, 630 W 168th. St., New York, NY 10032, USA. aa900@columbia.edu
Flint Beal
M
M
D000818:Animals; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human