title: Possible alterations in β-Synuclein, the non-amyloidogenic homologue of α-Synuclein, during progression of sporadic α-synucleinopathies.
abstract: α-Synucleinopathies are neurodegenerative disorders that are characterized by progressive decline of motor and non-motor dysfunctions. α-Synuclein (αS) has been shown to play a causative role in neurodegeneration, but the pathogenic mechanisms are still unclear. Thus, there are no radical therapies that can halt or reverse the disease's progression. β-Synuclein (βS), the non-amyloidogenic homologue of αS, ameliorates the neurodegeneration phenotype of αS in transgenic (tg) mouse models, as well as in cell free and cell culture systems, which suggests that βS might be a negative regulator of neurodegeneration caused by αS, and that "loss of function" of βS might be involved in progression of α-synucleinopathies. Alternatively, it is possible that "toxic gain of function" of wild type βS occurs during the pathogenesis of sporadic α-synucleinopathies, since tg mice expressing dementia with Lewy bodies-linked P123H βS develop progressive neurodegeneration phenotypes, such as axonal pathology and dementia. In this short review, we emphasize the aspects of "toxic gain of function" of wild type βS during the pathogenesis of sporadic α-synucleinopathies.
authors.affiliation: Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa Setagaya-ku Tokyo 156-0057, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa Setagaya-ku Tokyo 156-0057, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Sekigawa
authors.affiliation: Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa Setagaya-ku Tokyo 156-0057, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sekiyama
authors.affiliation: Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa Setagaya-ku Tokyo 156-0057, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takamatsu
authors.affiliation: Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa Setagaya-ku Tokyo 156-0057, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D018450:Disease Progression; D016631:Lewy Bodies / Q000235:genetics*; D020961:Lewy Body Disease / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics*; D051846:beta-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein; D051846:beta-Synuclein
keywords: dementia with Lewy bodies; toxic gain of function; α-synuclein; α-synucleinopathies; β-synuclein