期刊
NEUROSCIENCE LETTERS
卷 454, 期 3, 页码 187-192出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2009.02.056
关键词
Parkinson's disease; alpha-Synuclein; Mitochondrion; Complex I; Brain
资金
- National Natural Science Foundation of China [30570646, 30430280]
- Ministry of Science and Technology of China [2006CB500701, 2006AA02A408]
- Natural Science Foundation of Beijing [7022011]
- Japan Society for the Promotion of Science (JSPS) [C11680774, B 14380363]
- Academic Human Resources Development in Institutions of Higher Learning
alpha-Synuclein (alpha-Syn) abnormality and mitochondrial deficiency are two major changes in the brain of patients with Parkinson's disease (PD). A link between ct-Syn and mitochondria in PD has been demonstrated by a recent study showing that accumulation of ct-Syn in the mitochondria, from the PD-vulnerable brain regions was associated with decreased complex I activity of these mitochondria. In this study, we examined the normal expressions of ct-Syn in mitochondria from different regions of the rat brain. We showed that alpha-Syn was highly expressed in the mitochondria in olfactory bulb, hippocampus, striatum, and thalamus, where the cytosolic alpha-Syn was also rich. However, the cerebral cortex and cerebellum were two exceptions, which contained rich cytosolic a-Syn but very low or even undetectable levels of mitochondrial ct-Syn. The close quantitative association between mitochondrial and cytosolic ct-Syn in most brain regions, suggests that the concentration of cytosolic a-Syn may determine the amount of alpha-Syn in mitochondria. This is partially supported by the in vitro experiment showing that incubation of alpha-Syn with endogenous alpha-Syn-undetectable cerebellar mitochondria caused a dose-dependent transport of alpha-Syn to the mitochondria. Moreover, we found that the inhibitory effect of alpha-Syn on complex I activity of mitochondrial respiratory chain was also dose-dependent. These results suggest that ct-Syn in mitochondria is differentially expressed in different brain regions and the background levels of mitochondrial alpha-Syn may be a potential factor affecting mitochondrial function and predisposing some neurons to degeneration. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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