Rinsho Shinkeigaku (Clinical Neurology)

The 50th Annual Meeting of the Japanese Society of Neurology

Exploration of pathogenesis and therapy development for ALS employing sporadic disease model

Fumiaki Tanaka, M.D.1), Masahiro Waza, M.D.1), Masahiko Yamamoto, M.D.2) and Gen Sobue, M.D.1)

1)Department of Neurology, Nagoya University Graduate School of Medicine
2)Department of Speech Pathology and Audiology, Aichi Gakuin University School of Health Science

The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remain poorly understood even now 140 years after the first description of the disease in 1869 by Jean-Martin Charcot. Exploration of pathogenesis of ALS has long been dependent on transgenic animal models with mutations in the copper/zinc superoxide dismutase 1 (SOD1) gene. However, the lack of therapeutic concordance between these animal models and human sporadic ALS patients is troubling. The reasons include that there might exist the differences of pathogenesis between sporadic and familial ALS and/or the disease models for sporadic ALS have not bee established. We have been working on screening motor neuron-specific genes critical for pathogenesis of sporadic ALS using cDNA microarray and laser capture microdissection techniques. Many of the resultant genes are of intense interest and may provide a powerful tool for determining the molecular mechanisms of sporadic ALS. In particular, dynactin-1, a major component of dynein/dynactin complex and several cell cycle-related genes are the targets of our research. Development and analysis of new disease models for sporadic ALS based on these genes will open an avenue for novel therapeutics.
Full Text of this Article in Japanese PDF (408K)

(CLINICA NEUROL, 49: 811－813, 2009)
key words: sporadic amyotrophic lateral sclerosis, gene expression analysis, disease model, dynactin-1

(Received: 21-May-09)