Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison St, Cohn Bldg Room 306, Chicago, IL, 60612, USA.
The Van Andel Research Institute, Grand Rapids, MI, USA.
J Neural Transm (Vienna). 2018 Mar;125(3):385-400. doi: 10.1007/s00702-017-1720-0. Epub 2017 Apr 22.
Proper understanding of the mechanism(s) by which α-synuclein misfolds and propagates may hold the key to unraveling the complex pathophysiology of Parkinson's disease. A more complete understanding of the disease itself, as well as establishing animal models that fully recapitulate pathological and functional disease progression, are needed to develop treatments that will delay, halt or reverse the disease course. Traditional neurotoxin-based animal models fail to mimic crucial aspects of Parkinson's and thus are not relevant for the study of neuroprotection and disease-modifying therapies. Therefore, a new era of animal models centered on α-synuclein has emerged with the utility of nonhuman primates in these studies beginning to become important. Indeed, disease modeling in nonhuman primates offers a more similar anatomical and genetic background to humans, and the ability to assess complex behavioral impairments that are difficult to test in rodents. Furthermore, results obtained from monkey studies translate better to applications in humans. In this review, we highlight the importance of α-synuclein in Parkinson's disease and discuss the development of α-synuclein based nonhuman primate models.
正确理解α-突触核蛋白错误折叠和传播的机制可能是揭示帕金森病复杂病理生理学的关键。为了开发能够延缓、阻止或逆转疾病进程的治疗方法，需要更全面地了解这种疾病本身，并建立能够充分再现病理和功能疾病进展的动物模型。基于传统神经毒素的动物模型无法模拟帕金森病的关键方面，因此对于神经保护和疾病修饰治疗的研究没有意义。因此，以α-突触核蛋白为中心的动物模型新时代已经出现，非人类灵长类动物在这些研究中的应用开始变得重要。事实上，非人类灵长类动物的疾病建模提供了与人类更相似的解剖学和遗传学背景，以及评估复杂行为障碍的能力，而这些在啮齿动物中很难测试。此外，从猴子研究中获得的结果更能转化为人类应用。在这篇综述中，我们强调了α-突触核蛋白在帕金森病中的重要性，并讨论了基于α-突触核蛋白的非人类灵长类动物模型的发展。
