title: [The role of parkin in Parkinson's disease].
abstract: Parkin (Parkinson juvenile disease protein 2) is a ~52 kDa (426 amino acid) enzyme protein, encoded by PARK2 gene and located on the 6q chromosome. It plays an important role in the ubiquitin-proteasome system and acts as a regulator of protein breakdown. Parkin is located in the cytoplasma until a sustained depolarization occurs as a result of which it is translocated to the mitochondrial surface and induces the degradation of various membrane proteins which are candidates for mitophagia. Parkin is essential for cellular mitochondrial integrity. Parkin mutation leads to the accumulation of missfolded, aggregated proteins and degenerated mitochondria. The role of these changes in the pathomechanism of neurodegenerative diseases is well-known. It was a general belief for a long time that Parkinson's disease is without genetic component a sporadic disease. In 1997 a point mutation was, however, discovered in the α-synuclein gene, which caused dominantly inherited parkinsonism. At least 10 other genes were thereafter detected the mutation or deletion of which cause monogenic parkinsonism. Parkin mutation is responsible for about 50% of familial cases and for 10 to 20% of youth cases. According to the present views the improper regulation of protein aggregation and a dysfunction of the ubiquitin-proteasome system may be the common pathway of sporadic and hereditary Parkinson's disease. In the future it might have therapeutic value that parkin has versatile neuroprotective activity (against α-synuclein toxicity, proteasomal dysfunction, oxidative stress, kainite-induced and dopamine-mediated toxicity) as a result of which any reduction of parkin level or activity may cause damage in neuronal integrity.
authors: Semmelweis Egyetem, Farmakológiai és Farmakoterápiás Intézet, Budapest, Hungary. miklya.ildiko@med.semmelweis-univ.hu.
authors: Ildikó
authors: I
authors: Miklya
authors: Patricia
authors: P
authors: Göltl
authors: Florencia
authors: F
authors: Hafenscher
authors: Noémi
authors: N
authors: Pencz
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D059647:Gene-Environment Interaction; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007608:Kainic Acid / Q000378:metabolism; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008928:Mitochondria / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
chemical_list: D004298:Dopamine; D047908:Intracellular Signaling Peptides and Proteins; D007608:Kainic Acid; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D046988:Proteasome Endopeptidase Complex; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human