Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USA.
Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA.
Int J Mol Sci. 2018 May 31;19(6):1637. doi: 10.3390/ijms19061637.
Progressive accumulation of misfolded amyloid proteins in intracellular and extracellular spaces is one of the principal reasons for synaptic damage and impairment of neuronal communication in several neurodegenerative diseases. Effective treatments for these diseases are still lacking but remain the focus of much active investigation. Despite testing several synthesized compounds, small molecules, and drugs over the past few decades, very few of them can inhibit aggregation of amyloid proteins and lessen their neurotoxic effects. Recently, the natural polyphenol curcumin (Cur) has been shown to be a promising anti-amyloid, anti-inflammatory and neuroprotective agent for several neurodegenerative diseases. Because of its pleotropic actions on the central nervous system, including preferential binding to amyloid proteins, Cur is being touted as a promising treatment for age-related brain diseases. Here, we focus on molecular targeting of Cur to reduce amyloid burden, rescue neuronal damage, and restore normal cognitive and sensory motor functions in different animal models of neurodegenerative diseases. We specifically highlight Cur as a potential treatment for Alzheimer's, Parkinson's, Huntington's, and prion diseases. In addition, we discuss the major issues and limitations of using Cur for treating these diseases, along with ways of circumventing those shortcomings. Finally, we provide specific recommendations for optimal dosing with Cur for treating neurological diseases.
淀粉样蛋白错误折叠的逐渐积累是导致几种神经退行性疾病中突触损伤和神经元通讯障碍的主要原因之一。尽管过去几十年已经测试了几种合成化合物、小分子和药物，但很少有药物能够抑制淀粉样蛋白的聚集并减轻其神经毒性作用。最近，天然多酚姜黄素（Cur）已被证明是几种神经退行性疾病的一种很有前途的抗淀粉样蛋白、抗炎和神经保护剂。由于其对中枢神经系统的多效作用，包括与淀粉样蛋白的优先结合，Cur 被吹捧为治疗与年龄相关的脑部疾病的有希望的治疗方法。在这里，我们专注于 Cur 的分子靶向，以减少淀粉样蛋白负担、挽救神经元损伤，并在不同的神经退行性疾病动物模型中恢复正常的认知和感觉运动功能。我们特别强调 Cur 作为治疗阿尔茨海默病、帕金森病、亨廷顿病和朊病毒病的潜在治疗方法。此外，我们还讨论了使用 Cur 治疗这些疾病的主要问题和局限性，以及克服这些缺点的方法。最后，我们为治疗神经疾病时使用 Cur 的最佳剂量提供了具体建议。
