DJ-1: a newcomer in Parkinson's disease pathology.
Parkinson's disease (PD) is a movement disorder of high prevalence in the elderly. It is characterized by a loss of dopaminergic neurons and the presence of intracytoplasmic inclusions named Lewy bodies. To date six familial PD-associated proteins have been identified so far. Some of them are implicated in the development of either autosomal dominant (alpha-synuclein and LRRK2 (leucine-rich repeat kinase 2/dardarin) or early-onset recessive (parkin, DJ-1, PINK1 (PTEN-induced kinase-1) and ATP13A2) PD forms. A number of genetic studies have shown that 50% of the recessive forms are linked to mutations on parkin gene, followed by PINK1 (8-15%) and DJ-1 (1%). The purpose of this review is to provide an overview of the emerging data on the cellular and molecular biology of DJ-1. DJ-1 is a ubiquitous protein that was first described as an oncogene. Nevertheless, after its association to monogenic PD a number considerable data aiming at understanding its implication in the physiopathology of PD was produced. This review will describe the main advances concerning the function of DJ-1. A considerable progress that was only possible due to a better understanding of DJ-1 structure, genetics, distribution and development of in vivo models. All these points along with the description of recent data showing the interaction of DJ-1 with other PD-associated proteins will be given.
da Costa
Cristine Alves
CA
IPMC, UMR6097/CNRS/UNSA, Equipe labellisée Fondation pour la Recherche Médicale, 660 Route des Lucioles, 06560, Valbonne, France. acosta@ipmc.cnrs.fr
D000818:Animals; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D000071617:Protein Deglycase DJ-1
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1