Molecular mechanisms of nigral neurodegeneration in Park2 and regulation of parkin protein by other proteins.
Most of the patients with Parkinson's disease (PD) are sporadic. However, Since identification of monogenic forms of PD, the contribution of genetic factors to the pathogenesis of sporadic PD is proposed as one of major risk factors. Indeed, this is supported by the demonstration of the high concordance in twins, increased risk among relatives of PD patients in case control and family studies. Thus, the functional analysis for the gene products for familial PD provides us a good hint to elucidate the pathogenesis of nigral degeneration. For example, although alpha-synuclein is involved in a rare dominant form of familial PD with dopa responsive parkinsonian features, this molecule is a major component of and Lewy bodies (LBs). In contrast, Park2 (parkin-related disease) is the most frequent form among patients with young-onset PD. However, Park2 brains generally lack the formation of LBs. In the other word, parkin responsible for Park2 is essential for the formation of LBs. Thus, both alpha-synuclein and parkin are speculated to share a common pathway. Here, we reviewed the parkin function and molecular mechanisms of Park2.
Hattori
N
N
Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan. nhattori@med.juntendo.ac.jp
Machida
Y
Y
Sato
S
S
Noda
K
K
Iijima-Kitami
M
M
Kubo
S
S
Mizuno
Y
Y
D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009410:Nerve Degeneration / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D010300:Parkinson Disease / Q000473:pathology*; D013378:Substantia Nigra / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics; D051844:alpha-Synuclein / Q000502:physiology
D009419:Nerve Tissue Proteins; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein