Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi 110042, India.
Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi 110042, India.
Neuropeptides. 2019 Dec;78:101971. doi: 10.1016/j.npep.2019.101971. Epub 2019 Sep 13.
Alzheimer's and Parkinson's diseases are one of the world's leading causes of death. >50 million people throughout the world are suffering with these diseases. They are two distinct progressive neurodegenerative disorders affecting different regions of the brain with diverse symptoms, including memory and motor loss respectively, but with the advancement of diseases, both affect the whole brain and exhibit some common biological symptoms. For instance, >50% PD patients develop dementia in their later stages, though it is a hallmark of Alzheimer's disease. In fact, latest research has suggested the involvement of some common pathophysiological and genetic links between these diseases, including the deposition of pathological Aβ, Tau, and α-synuclein in both the cases. Therefore, it is pertinent to diagnose the shared biomarkers, their aggregation mechanism, their intricate relationships in the pathophysiology of disease and therapeutic markers to target them. This would enable us to identify novel markers for the early detection of disease and targets for the future therapies. Herein, we investigated molecular aspects of Aβ, Tau, and α-Synuclein aggregation, and characterized their functional partners involved in the pathology of AD and PD. Moreover, we identified the molecular-crosstalk between AD and PD associated with their pathogenic proteins- Aβ, Tau, and α-Synuclein. Furthermore, we characterized their ubiquitinational enzymes and associated interaction network regulating the proteasomal clearance of these pathological proteins.
阿尔茨海默病和帕金森病是世界上主要的死亡原因之一。全球有超过 5000 万人患有这些疾病。它们是两种不同的进行性神经退行性疾病，分别影响大脑的不同区域，具有不同的症状，包括记忆和运动功能丧失，但随着疾病的发展，两者都会影响整个大脑，并表现出一些共同的生物学症状。例如，超过 50%的 PD 患者在晚期会发展为痴呆症，尽管这是阿尔茨海默病的一个标志。事实上，最新的研究表明，这些疾病之间存在一些共同的病理生理和遗传联系，包括在两种情况下病理性 Aβ、Tau 和 α-突触核蛋白的沉积。因此，诊断共同的生物标志物、它们的聚集机制、它们在疾病病理生理学中的复杂关系以及治疗靶点是很重要的。这将使我们能够识别疾病早期检测的新标志物和未来治疗的靶点。在这里，我们研究了 Aβ、Tau 和 α-突触核蛋白聚集的分子方面，并描述了它们在 AD 和 PD 病理中的功能伙伴。此外，我们确定了与 AD 和 PD 相关的分子串扰及其与致病性蛋白 Aβ、Tau 和 α-突触核蛋白有关。此外，我们还描述了它们的泛素化酶及其相关的相互作用网络，这些网络调节这些病理性蛋白的蛋白酶体清除。
