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Neuropathology and omics in motor neuron diseases

Authors

  • Fumiaki Tanaka,

    Corresponding author
    1. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya
      Fumiaki Tanaka, MD, PhD, Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Email: ftanaka@med.nagoya-u.ac.jp
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  • Kensuke Ikenaka,

    1. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya
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  • Masahiko Yamamoto,

    1. Department of Speech Pathology and Audiology, Aichi Gakuin University School of Health Science, Aichi
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  • Gen Sobue

    1. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya
    2. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama, Japan
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Fumiaki Tanaka, MD, PhD, Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Email: ftanaka@med.nagoya-u.ac.jp

Abstract

Motor neuron diseases, including amyotrophic lateral sclerosis (ALS), are devastating disorders and effective therapies have not yet been established. One of the reasons for this lack of therapeutics, especially in sporadic ALS (SALS), is attributed to the absence of excellent disease models reflecting its pathology. For this purpose, identifying important key molecules for ALS pathomechanisms and developing disease models is crucial, and omics approaches, including genomics, transcriptomics and proteomics, have been employed. In particular, transcriptome analysis using cDNA microarray is the most popular omics approach and we have previously identified dynactin-1 as an important molecule downregulated in the motor neurons of SALS patients from the early stage of the disease. Dynactin-1 is also known as a causative gene in familial ALS (FALS). Dynactin-1 is a major component of the dynein/dynactin motor protein complex functioning in retrograde axonal transport. In motor neuron diseases as well as other neurodegenerative diseases, the role of axonal transport dysfunction in their pathogenesis always draws attention, but its precise mechanisms remain to be fully elucidated. In this article, we review our previous omics approach to SALS and the role of dynactin-1 in the pathogenesis of ALS. Finally, we emphasize the need for creating novel SALS disease models based on the results of omics analysis, especially based on the observation that dynactin-1 gene expression was downregulated in SALS motor neurons.

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