The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine neuron degeneration.
The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine neuron degeneration.
复制标题
DOI：
10.1111/jnc.12072
复制
发表时间：
2013-01
影响因子：
4.7
通讯作者：
Nass R
中科院分区：
文献类型：
--
作者：
VanDuyn N;Settivari R;LeVora J;Zhou S;Unrine J;Nass R
Aluminum (Al3+) is the most prevalent metal in the earth's crust, and is a known human neurotoxicant. Al3+ has been shown to accumulate in the substantia nigra of Parkinson's disease (PD) patients, and epidemiological studies suggest correlations between Al3+ exposure and the propensity to develop both PD and the amyloid plaque-associated disorder Alzheimer's disease (AD). Although Al3+ exposures have been associated with the development of the most common neurodegenerative disorders, the molecular mechanism involved in Al3+ transport in neurons and subsequent cellular death has remained elusive. In this study we show that a brief exposure to Al3+ decreases mitochondrial membrane potential and cellular ATP levels, and confers dopamine (DA) neuron degeneration in the genetically tractable nematode Caenorhabditis elegans (C. elegans). Al3+ exposure also exacerbates DA neuronal death conferred by the human PD-associated protein α-synuclein. DA neurodegeneration is dependent on SMF-3, a homologue to the human divalent metal transporter (DMT-1), as a functional null mutation partially inhibits the cell death. We also show that SMF-3 is expressed in DA neurons, Al3+ exposure results in a significant decrease in protein levels, and the neurodegeneration is partially dependent on the PD-associated transcription factor Nrf2/SKN-1 and caspase Apaf1/CED-4. Furthermore we provide evidence that the deletion of SMF-3 confers Al3+-resistance due to sequestration of Al3+ into an intracellular compartment. This study describes a novel model for Al3+-induced DA neurodegeneration and provides the first molecular evidence of an animal Al3+ transporter.
登录
查看更多内容
影响因子：
3.4
作者：
EHRENBERG, B;MONTANA, V;LOEW, LM
通讯作者：
LOEW, LM
影响因子：
4.7
作者：
Lakso, M;Vartiainen, S;Wong, G
通讯作者：
Wong, G
影响因子：
5.8
作者：
Larkin, M. A.;Blackshields, G.;Higgins, D. G.
通讯作者：
Higgins, D. G.
DOI：
10.1073/pnas.92.22.10089
发表时间：
1995-10-24
影响因子：
11.1
作者：
CELLIER, M;PRIVE, G;GROS, P
通讯作者：
GROS, P
影响因子：
3.5
作者：
Lastres-Becker, Isabel;Ulusoy, Ayse;Cuadrado, Antonio
通讯作者：
Cuadrado, Antonio