International Journal of Biological Sciences

Impact factor
3.873

ISSN 1449-2288

News feeds of IJBS published articles
My Manuscript
My Account

Journal of Biomedicinenew

Theranostics

International Journal of Medical Sciences

Journal of Cancer

Oncomedicine

Journal of Genomics

Journal of Bone and Joint Infection (JBJI)

Nanotheranostics

Journal of Genomics now in PubMed/PubMed Central. Submit manuscript...

PubMed Central Indexed in Journal Impact Factor

Int J Biol Sci 2011; 7(2):234-243. doi:10.7150/ijbs.7.234

Research Paper

TDP-43 Potentiates Alpha-synuclein Toxicity to Dopaminergic Neurons in Transgenic Mice

Tian Tian1, 2*, Cao Huang1*, Jianbin Tong1, Ming Yang1, Hongxia Zhou1✉, Xu-Gang Xia1

1. Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA
2. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China
*These authors contributed equally to this work.

Abstract

TDP-43 and α-synuclein are two disease proteins involved in a wide range of neurodegenerative 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 proteinopathy 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 overexpression of normal TDP-43 and mutant α-synuclein caused a more severe loss of dopaminergic 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.

Keywords: TDP-43, alpha-synuclein, mice, dopaminergic neuron, Parkinson's disease, frontotemporal lobe degeneration, genetic model

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Tian T, Huang C, Tong J, Yang M, Zhou H, Xia XG. TDP-43 Potentiates Alpha-synuclein Toxicity to Dopaminergic Neurons in Transgenic Mice. Int J Biol Sci 2011; 7(2):234-243. doi:10.7150/ijbs.7.234. Available from http://www.ijbs.com/v07p0234.htm