Targeting the progression of Parkinson's disease.
Targeting the progression of Parkinson's disease.
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DOI：
10.2174/157015909787602814
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发表时间：
2009-03
影响因子：
5.3
通讯作者：
Finkelstein DI
中科院分区：
文献类型：
--
作者：
George JL;Mok S;Moses D;Wilkins S;Bush AI;Cherny RA;Finkelstein DI
当患者在诊所首次出现帕金森病症状时，黑质（SN）中相当大比例（50-70%）的细胞已经被破坏。这种退化会持续下去，直到几年内大部分细胞死亡。除了罕见的家族性PD病例外，细胞丢失的最初触发因素尚不清楚。然而，我们确实有一些线索，说明为什么损害一旦开始，就会有增无减。这将代表治疗的一个重大进展，即在患者首次出现在诊所的阶段阻止细胞损失。目前帕金森病的治疗集中在缓解疾病的运动症状，不幸的是，随着神经变性和症状的进展，这些治疗失去了效果。目前正在研究许多实验方法，试图改变疾病的进展。这些范围从丢失的神经元的神经保护疗法的替代，这些将在这篇评论中简要讨论。这篇综述的主旨是探讨多巴胺，α突触核蛋白和氧化还原活性金属之间的相互作用。有大量证据表明，SN细胞的破坏是由于涉及多巴胺、α突触核蛋白和氧化还原活性金属的一系列自传播反应而发生的。作为一种有效的还原剂，神经递质多巴胺在该方案中起着核心作用，通过氧化还原金属化学作用来催化α-突触核蛋白的毒性寡聚体和包括6-羟基多巴胺在内的神经毒性代谢物的形成。据推测，这些饲料循环的神经变性产生进一步的氧化应激。解剖和理解观察到的病理变化的目的是确定治疗靶点，以减轻这种使人衰弱的疾病的进展。
By the time a patient first presents with symptoms of Parkinson’s disease at the clinic, a significant proportion (50-70%) of the cells in the substantia nigra (SN) has already been destroyed. This degeneration progresses until, within a few years, most of the cells have died. Except for rare cases of familial PD, the initial trigger for cell loss is unknown. However, we do have some clues as to why the damage, once initiated, progresses unabated. It would represent a major advance in therapy to arrest cell loss at the stage when the patient first presents at the clinic. Current therapies for Parkinson’s disease focus on relieving the motor symptoms of the disease, these unfortunately lose their effectiveness as the neurodegeneration and symptoms progress. Many experimental approaches are currently being investigated attempting to alter the progression of the disease. These range from replacement of the lost neurons to neuroprotective therapies; each of these will be briefly discussed in this review. The main thrust of this review is to explore the interactions between dopamine, alpha synuclein and redox-active metals. There is abundant evidence suggesting that destruction of SN cells occurs as a result of a self-propagating series of reactions involving dopamine, alpha synuclein and redox-active metals. A potent reducing agent, the neurotransmitter dopamine has a central role in this scheme, acting through redox metallo-chemistry to catalyze the formation of toxic oligomers of alpha-synuclein and neurotoxic metabolites including 6-hydroxydopamine. It has been hypothesized that these feed the cycle of neurodegeneration by generating further oxidative stress. The goal of dissecting and understanding the observed pathological changes is to identify therapeutic targets to mitigate the progression of this debilitating disease.
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影响因子：
2.5
作者：
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