| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Recently, we showed that NUB1 is a synphilin-1-interacting protein and that NUB1, as well as synphilin-1, accumulates in Lewy bodies in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and glial cytoplasmic inclusions in multiple system atrophy (MSA). In this study, an investigation was further conducted to elucidate the immunohistochemical localization of NUB1 in various neurodegenerative disorders. In controls, anti-NUB1 antibody weakly immunolabeled the neuronal perikarya. In PD and DLB, cortical and brainstem-type Lewy bodies, pale bodies and Lewy neurites were strongly immunolabeled with anti-NUB1. In MSA, NUB1 immunoreactivity was found in the intracytoplasmic inclusions of both neuronal and oligodendroglial cells, neuronal nuclear inclusions, and swollen neurites. No NUB1 immunoreactivity was found in a variety of other neuronal or glial inclusions in other disorders, including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degener
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ation, motor neuron disease and triplet-repeat diseases. These findings indicate that the abnormal accumulation of NUB! is specific for α-synucleinopathy lesions.
Next, we immunohistochemically examined the neostriatum from 25 patients with symptomatic and presymptomatic PD with various degrees of Lewy body pathology, using anti-phosphorylated α-synuclein (αS) antibody. These patients were classified, according to the PD staging proposed by Braak et al. αS immunohistochemistry revealed neuronal and glial cytoplasmic inclusions and neuritic changes in the neostriatum. αS inclusions were found in the medium-sized neurons (GABAergic neurons that project to the globus pallidus) and large neurons (cholinergic interneurons); the former began to appear at stage III and the latter was noted at stages V and VI. Neuritic changes and glial inclusions also began to appear at stage III. The numbers of neuronal and glial inclusions and the extent of neuritic changes correlated with the PD stage (p<0.001). These findings-suggest that intrinsic neostriatal neurons degenerate through αS aggregation during PD progression. Less
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