TDP-43 potentiates alpha-synuclein toxicity to dopaminergic neurons in transgenic mice Article

Tian, T, Huang, C, Tong, J et al. (2011). TDP-43 potentiates alpha-synuclein toxicity to dopaminergic neurons in transgenic mice . 7(2), 234-243. 10.7150/ijbs.7.234

cited authors

  • Tian, T; Huang, C; Tong, J; Yang, M; Zhou, H; Xia, XG

authors

abstract

  • TDP-43 and α-synuclein are two disease proteins involved in a wide range of neurodegen-erative diseases. While TDP-43 proteinopathy is considered a pathologic hallmark of sporadic amyotrophic lateral sclerosis and frontotemporal lobe degeneration, α-synuclein is a major component of Lewy body characteristic of Parkinson's disease. Intriguingly, TDP-43 protei-nopathy also coexists with Lewy body and with synucleinopathy in certain disease conditions. Here we reported the effects of TDP-43 on α-synuclein neurotoxicity in transgenic mice. Overexpression of mutant TDP-43 (M337V substitution) in mice caused early death in transgenic founders, but overexpression of normal TDP-43 only induced a moderate loss of cortical neurons in the transgenic mice at advanced ages. Interestingly, concomitant over-expression of normal TDP-43 and mutant α-synuclein caused a more severe loss of dopa-minergic neurons in the double transgenic mice as compared to single-gene transgenic mice. TDP-43 potentiated α-synuclein toxicity to dopaminergic neurons in living animals. Our finding provides in vivo evidence suggesting that disease proteins such as TDP-43 and α-synuclein may play a synergistic role in disease induction in neurodegenerative diseases. © Ivyspring International Publisher.

publication date

  • January 1, 2011

Digital Object Identifier (DOI)

start page

  • 234

end page

  • 243

volume

  • 7

issue

  • 2