Regulatory Mechanisms and Physiological Significance of Reelin Function

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  • Kohno Takao
    Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University

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  • 巨大分泌タンパク質リーリンの機能制御機構と生理的意義の解明
  • キョダイ ブンピ タンパクシツ リーリン ノ キノウ セイギョ キコウ ト セイリテキ イギ ノ カイメイ

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Abstract

 Reelin is a large secreted glycoprotein that regulates embryonic neuronal lamination and adult synaptic function. Secreted Reelin binds to lipoprotein receptors expressed on neurons. The Reelin-receptor interaction induces phosphorylation of an intracellular adaptor protein Dab1, which is required for normal embryonic brain development and adult brain functions. It has been suggested that Reelin hypofunction plays a role in the pathogenesis of several neuropsychiatric diseases, such as schizophrenia, autism, and Alzheimer's disease. Thus upregulation of Reelin activity may ameliorate the symptoms of neuropsychiatric diseases. However, the regulatory mechanism underlying the functions of Reelin is largely unknown and there are no good animal models of Reelin malfunction; thus, causal relations between Reelin and neuropsychiatric diseases remain unclear. Recently, our studies have shown that proteolytic cleavage of the Reelin protein regulates its activity. Herein, we will review recent findings about relations between Reelin and Alzheimer's disease, and the mechanism underlying the regulation of Reelin function by proteolytic cleavage. Also, we will discuss the prospect of treating neuropsychiatric diseases by upregulation of Reelin activity.<br>

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  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 137 (10), 1233-1240, 2017-10-01

    The Pharmaceutical Society of Japan

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