Sidhu Anita, Wersinger Christophe, Vernier Philippe
Department of Pediatrics, Georgetown University, Washington, DC, USA.
FASEB J. 2004 Apr;18(6):637-47. doi: 10.1096/fj.03-1112rev.
alpha-Synuclein is a key component of the pathological process of neurodegeneration in Parkinson's disease. Although its contributions to normal physiological conditions remain elusive, converging observations suggest that a primary function of this protein in dopaminergic neurons may be the regulation of dopamine content and synaptic tone at the synapse. We review here cumulative evidence that demonstrates the participation of alpha-synuclein in the life cycle of dopamine from its synthesis, storage, release, and reuptake. The regulatory role of alpha-synuclein on dopamine metabolism is assessed by discussing the experimental evidence supporting each of these observations in the healthy physiological maintenance of dopaminergic neurons, as well as showing how disruption of these events can initiate the observed neurotoxicity of alpha-synuclein and the genesis of the degenerative processes associated with Parkinson's disease.
α-突触核蛋白是帕金森病神经退行性病变病理过程的关键组成部分。尽管其在正常生理状态下的作用仍不明确，但越来越多的观察结果表明，该蛋白在多巴胺能神经元中的主要功能可能是调节突触处的多巴胺含量和突触张力。我们在此综述了累积证据，这些证据证明了α-突触核蛋白参与了多巴胺从合成、储存、释放到再摄取的整个生命周期。通过讨论支持这些观察结果的实验证据，评估了α-突触核蛋白对多巴胺代谢的调节作用，这些证据涉及多巴胺能神经元在健康生理维持中的作用，同时也展示了这些过程的破坏如何引发α-突触核蛋白所观察到的神经毒性以及与帕金森病相关的退行性过程的发生。
