Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.
Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.
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DOI：
10.1016/j.brainresbull.2017.03.009
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发表时间：
2017-07
影响因子：
3.8
通讯作者：
Franco R
中科院分区：
文献类型：
--
作者：
Anandhan A;Jacome MS;Lei S;Hernandez-Franco P;Pappa A;Panayiotidis MI;Powers R;Franco R
帕金森病（PD）的病理特征是黑质多巴胺能神经元的丢失和蛋白质内含物（路易体）的积聚。PD由遗传改变、环境/职业暴露和衰老引发。然而，将这些PD风险因素与神经元功能障碍联系起来的确切分子机制仍不清楚。氧化还原稳态和生物能量学的改变（能量衰竭）被认为是神经变性的中心组成部分，其导致多巴胺能细胞中重要的稳态过程的损害，例如蛋白质质量控制机制、神经递质释放/代谢、囊泡的轴突运输和细胞存活。重要的是，生物能量学和氧化还原稳态都与神经胶质细胞的中央碳代谢有关。我们和其他人最近已经建立了一个联系，在中央碳代谢的变化引起的PD危险因素，氧化还原稳态和生物能量学和它们的贡献多巴胺能细胞的生存/死亡。本文就PD中代谢功能障碍、能量衰竭和氧化还原失衡之间的关系进行综述，重点阐述中心碳（葡萄糖）代谢的作用。这里总结的证据强烈支持PD作为细胞代谢紊乱的考虑。
The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson’s disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic process in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism.
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影响因子：
4.3
作者：
Allaman I;Bélanger M;Magistretti PJ
通讯作者：
Magistretti PJ
影响因子：
4.3
作者：
Annesley SJ;Lay ST;De Piazza SW;Sanislav O;Hammersley E;Allan CY;Francione LM;Bui MQ;Chen ZP;Ngoei KR;Tassone F;Kemp BE;Storey E;Evans A;Loesch DZ;Fisher PR
通讯作者：
Fisher PR
影响因子：
--
作者：
AMBANI, LM;VANWOERT, MH;MURPHY, S
通讯作者：
MURPHY, S
影响因子：
7.4
作者：
Baxter, Paul S.;Hardingham, Giles E.
通讯作者：
Hardingham, Giles E.
影响因子：
3.7
作者：
Abramov AY;Gegg M;Grunewald A;Wood NW;Klein C;Schapira AH
通讯作者：
Schapira AH