The parkinsonian mimetic, MPP+, specifically impairs mitochondrial transport in dopamine axons.
The parkinsonian mimetic, MPP+, specifically impairs mitochondrial transport in dopamine axons.
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DOI：
10.1523/jneurosci.0711-11.2011
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发表时间：
2011-05-11
期刊：
影响因子：
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通讯作者：
O'Malley KL
中科院分区：
文献类型：
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作者：
Kim-Han JS;Antenor-Dorsey JA;O'Malley KL
Impaired axonal transport may play a key role in Parkinson’s disease. To test this notion, a microchamber system was adapted to segregate axons from cell bodies using green fluorescent protein-labeled mouse dopamine (DA) neurons. Transport was examined in axons challenged with the DA neurotoxin MPP+. MPP+ rapidly reduced overall mitochondrial motility in DA axons; among motile mitochondria, anterograde transport was slower yet retrograde transport was increased. Transport effects were specific for DA mitochondria, which were smaller and transported more slowly than their non-DA counterparts. MPP+ did not affect synaptophysin-tagged vesicles or any other measureable moving particle. Toxin effects on DA mitochondria were not dependent upon ATP, calcium, free radical species, JNK, or caspase3/PKC pathways but were completely blocked by the thiol-anti-oxidant N-acetyl-cysteine or membrane-permeable glutathione. Since these drugs also rescued processes from degeneration, these findings emphasize the need to develop therapeutics aimed at axons as well as cell bodies to preserve “normal” circuitry and function as long as possible.
