2010 Fiscal Year Final Research Report
The analysis of the mechanism of the nuclear translocation disorder in ALS
| Project/Area Number |
21790843
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Kyushu University |
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Principal Investigator |
TAKAHISA Tateishi Kyushu University, 医学研究院, 助教 (50423546)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 脳神経疾患 / 神経化学 / 神経病理学 / 筋萎縮性側索硬化症 |
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| Research Abstract |
We measured the levels of 27 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) from 42 patients with sporadic amyotrophic lateral sclerosis (ALS) and 34 control patients with non-inflammatory neurological diseases (OND), using a multiplexed fluorescent bead-based immunoassay. Among cytokines/chemokines elevated in ALS, CCL2 and CXCL8 levels were negatively correlated with the revised ALS functional rating scale (ALSFRS-R) score, while CCL4 showed a positive correlation with ALSFRS-R score. CCL4 and CXCL10 showed negative correlations with disease progression rate. These chemokine alterations are assumed to somehow correlate with the clinical course of ALS.
We carried out clinical, neuropathological, and genetic studies on a large Japanese pedigree with familial ALS. In six successive generations of this family, 16 individuals of both sexes were affected by progressive muscle atrophy and weakness, indicating an autosomal dominant trait. The missense mutation c.1561 C>T (p.R521C) was found in exon 15 of FUS in the four patients examined. Neuropathological study of one autopsied case with the FUS mutation revealed multiple system degeneration in addition to upper and lower motor neuron involvement: the globus pallidus, thalamus, substantia nigra, cerebellum, inferior olivary nucleus, solitary nucleus, intermediolateral horn, Clarke's column, Onuf's nucleus, central tegmental tract, medial lemniscus, medial longitudinal fasciculus, superior cerebellar peduncle, posterior column, and spinocerebellar tract were all degenerated. Argyrophilic and basophilic neuronal or glial cytoplasmic inclusions immunoreactive for FUS, GRP78/BiP, p62, and ubiquitin were detected in affected lesions. The FUS R521C mutation in this Japanese family caused familial ALS with pathological features of multiple system degeneration and neuronal basophilic inclusions.
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[Journal Article] Multiple system degeneration with basophilic inclusions in Japanese ALS patients with FUS mutation.2010
Author(s)
Tateishi T, Hokonohara T, Yamasaki R, Miura S, Kikuchi H, Iwaki A, Tashiro H, Furuya H, Nagara Y, Ohyagi Y, Nukina N, Iwaki T, Fukumaki Y, Kira J
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Journal Title
Acta Neuropathologica.(Berl). 119
Pages: 355-364
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