A β-synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain

Masayo Fujita, Shuei Sugama, Kazunari Sekiyama, Akio Sekigawa, Tohru Tsukui, Masaaki Nakai, Masaaki Waragai, Takato Takenouchi, Yoshiki Takamatsu, Jianshe Wei, Edward Rockenstein, Albert R. LaSpada, Eliezer Masliah, Satoshi Inoue and Makoto Hashimoto ()
Additional contact information
Masayo Fujita: Tokyo Metropolitan Institute for Neuroscience
Shuei Sugama: Tokyo Metropolitan Institute for Neuroscience
Kazunari Sekiyama: Tokyo Metropolitan Institute for Neuroscience
Akio Sekigawa: Tokyo Metropolitan Institute for Neuroscience
Tohru Tsukui: Research Center for Genomic Medicine, Saitama Medical University
Masaaki Nakai: Tokyo Metropolitan Institute for Neuroscience
Masaaki Waragai: Tokyo Metropolitan Institute for Neuroscience
Takato Takenouchi: Tokyo Metropolitan Institute for Neuroscience
Yoshiki Takamatsu: Tokyo Metropolitan Institute for Neuroscience
Jianshe Wei: Tokyo Metropolitan Institute for Neuroscience
Edward Rockenstein: University of California-San Diego
Albert R. LaSpada: University of California-San Diego
Eliezer Masliah: University of California-San Diego
Satoshi Inoue: Research Center for Genomic Medicine, Saitama Medical University
Makoto Hashimoto: Tokyo Metropolitan Institute for Neuroscience

Nature Communications, 2010, vol. 1, issue 1, 1-9

Abstract: Abstract The discovery of α-synuclein (αS) mutations has made a major contribution to the understanding of the pathogenesis of α-synucleinopathies such as Parkinson's disease and dementia with Lewy bodies (DLB). In contrast, less attention has been paid to β-synuclein (βS) mutations. In this paper, we show that transgenic (tg) mice expressing DLB-linked P123H βS develop progressive neurodegeneration, as characterized by axonal swelling, astrogliosis and behavioural abnormalities, with memory disorder being more prominent than motor deficits. Furthermore, cross-breeding of P123H βS tg mice with αS tg mice, but not with αS knockout mice, greatly enhanced neurodegeneration phenotypes. These results suggest that P123H βS is pathogenic and cooperates with pathogenic αS to stimulate neurodegeneration in mouse brain, indicating a causative role of P123H βS in familial DLB. Given the neuritic pathology of βS in sporadic α-synucleinopathies, it appears that alteration of βS can contribute to the pathogenesis of a broad range of α-synucleinopathies.

Date: 2010
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms1101 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:1:y:2010:i:1:d:10.1038_ncomms1101

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1101

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().