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Recent Patents on Regenerative Medicine
ISSN (Print): 2210-2965
ISSN (Online): 2210-2973
VOLUME: 2
ISSUE: 1
DOI: 10.2174/2210296511202010030









Perspectives on Therapeutic Target for Multiple System Atrophy

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Author(s): Ikuru Yazawa
Pages 30-36 (7)
Abstract:
Multiple system atrophy (MSA) is a neurodegenerative disease in which oligodendrocytes and neurons in the central nervous system (CNS) are affected. MSA is characterized by abnormal α-synuclein inclusions in oligodendrocytes, which are diagnostic of MSA. Formation of α-synuclein inclusions may be the primary lesions that eventually compromise neuronal function and viability. But little is known about the cellular mechanisms by which oligodendrocytic α- synuclein inclusions cause neuronal degeneration in MSA. Transgenic mice in which human wild-type α-synuclein was overexpressed in oligodendrocytes were generated as animal models of MSA. Oligodendrocytic inclusions induced neuronal accumulation of α-synuclein and progressive neuronal degeneration in the mouse CNS. In mouse neurons, endogenous α-synuclein binds to β-III tubulin in microtubules to form insoluble protein complexes, leading to neuronal dysfunction. The findings with mouse models suggest three pathological processes to underlie neurodegeneration in MSA: increase in neuronal expression of α-synuclein by oligodendrocytic inclusions, induction of neuronal accumulation of insoluble protein complexes by binding of α-synuclein to β-III tubulin and disturbance of α-synuclein modulation by neuronal activity. A positive perspective on the therapeutic target for MSA has been recently proposed. The methods to inhibit α-synuclein accumulation and those disclosed in related recent patent applications are summarized in this review.
Keywords:
inclusion, microtubule, mouse model, Multiple system atrophy (MSA), neurodegeneration, neuronal dysfunction, oligodendrocyte, α-synuclein, central nervous system (CNS), oligodendrocytes
Affiliation:
Laboratory of Research Resources, Research Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka-cho, Obu-shi, Aichi 474-8511, Japan.