Familial Parkinson's disease. Alpha-synuclein and parkin.
We have reviewed recent progress in establishing the function of alpha-synuclein and parkin in relation to nigral degeneration in autosomal dominant and autosomal recessive PD. Mutations of alpha-synuclein (Ala53Thr and Ala30Pro) cause a form of autosomal dominant PD with early onset. Parkin is a novel protein expressed in the cytoplasm, including the terminal regions and Golgi apparatus. Mutations of parkin cause a form of autosomal recessive young-onset PD (ARJP). Both proteins appear to be associated with fast axonal transport. In addition, in sporadic PD, normal alpha-synuclein shows an increased tendency to self-aggregate. Thus, altered axonal transport of presynaptic proteins appears to play a crucial role in neurodegeneration in PD.
Mizuno
Y
Y
Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Hattori
N
N
Kitada
T
T
Matsumine
H
H
Mori
H
H
Shimura
H
H
Kubo
S
S
Kobayashi
H
H
Asakawa
S
S
Minoshima
S
S
Shimizu
N
N
D006801:Humans; D008025:Ligases / Q000235:genetics*; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology; D051843:Synucleins; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases