Toshiaki Kitami

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Mutational dysfunction of PARKIN gene, which encodes a double RING finger protein and has ubiquitin ligase E3 activity, is the major cause of autosomal recessive juvenile Parkinsonism. Although many studies explored the functions of Parkin, its biochemical character is poorly understood. To address this issue, we established an E3 assay system using(More)
OBJECTIVE Recently, genomic multiplications of alpha-synuclein gene (SNCA) have been reported to cause hereditary early-onset parkinsonism. The objective of this study was to assess the frequency of SNCA multiplications among autosomal dominant hereditary Parkinson's disease (ADPD). METHODS We screened 113 ADPD probands and 200 sporadic PD cases by(More)
In this report, we evaluated the allele frequency of the D/N394 single nucleotide polymorphism (SNP) in exon 11 of the parkin gene in 200 Japanese patients with sporadic Parkinson's disease (PD) and 200 normal controls. Although the reported allele frequency of G-to-A (D/N394) is 2% in Caucasians, this SNP was not detected in Japanese patients and healthy(More)
Lewy bodies (LBs) are the pathologic hallmark of Parkinson's disease. Recent studies revealed that LBs exhibit several morphologic and molecular similarities to aggresomes. Aggresomes are perinuclear aggregates representing intracellular deposits of misfolded proteins. Recently, valosin-containing protein (VCP) was one of the components of LBs, suggesting(More)
Ubiquitin is one of the major components of Lewy bodies (LB), the pathological hallmark of Parkinson's disease (PD). Here, we identified that a phosphorylated form of IkappaBalpha (pIkappaBalpha), an inhibitor of NF-kappaB, and SCF(beta-TrCP), the ubiquitin ligase of pIkappaBalpha, are components of LB in brains of PD patients. In vitro studies identified(More)
Considering the involvement of ubiquitin-proteasome system (UPS) in Parkinson's disease (PD), the aim of the present study was to determine the distribution of proteasomes in PD brains. Immunohistochemical studies showed localization of 20S proteasome in the nuclei of neurons of the putamen and substantia nigra of PD. In contrast, no nuclear staining was(More)
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