Interactions of Protein Aggregation in Parkinson's Dementia

帕金森氏病（Parkinson's disease，PD）是最常见的神经退行性运动障碍，它与帕金森氏病（Parkinson's disease，PD）有许多共同点。 共同特征，如蛋白质聚集，与神经退行性疾病的范围更广。PD 可能出现额外的临床损伤，痴呆在PD患者中很常见。尽管 中脑中特定多巴胺能神经元的丢失在很大程度上是大多数多巴胺能神经元死亡的原因。 帕金森病的运动功能障碍，导致神经元死亡的机制还不清楚。 虽然家族性PD相对较常见，但α-突触核蛋白基因突变的鉴定已导致 发现这种蛋白质是疾病特征性包含物（称为Lewy）的主要成分 尸体和路易神经突α-突触核蛋白通常是一种可溶性蛋白，但它可以溶解成10-15 nm， 具有特定生物物理特性的纤维称为“淀粉样蛋白”，以形成病理性内含物。病理 内含物，如细胞内神经原纤维缠结和细胞外Abeta肽沉积物， 阿尔茨海默氏病的特征，经常伴随α-突触核蛋白聚集体。 事实上，apha-突触核蛋白和tau包涵体可以发生在同一细胞中，通常相互交织。阿尔法synuclein 已经显示能够作为tau聚集的诱导剂，并且两种蛋白质都可以增强tau蛋白的聚集。 一旦这个过程开始，彼此聚合。然而，分子机制和 导致该过程的生理变化尚未阐明。试管实验和 将进行转基因小鼠研究以解决这些问题。将进行研究，以评估 由α-突触核蛋白和tau蛋白引起的转基因小鼠的选择性脆弱性和行为障碍 相互作用导致病理后果的形成。异常的生理变化，例如 作为硝化损伤和过度磷酸化，可能参与介导α-突触核蛋白和tau蛋白 将研究这些相互作用和机制。Abeta肽的转基因小鼠模型 沉积物也将用于评估可能的病理机制， 促进α-突触核蛋白聚集。这些发现提供了重要的信息机制 以及导致α-突触核蛋白和tau包涵体形成的生理变化，并可能导致 在规划有效的治疗方法的见解。

Parkinson's disease (PD), is the most common neurodegenerative movement disorder, and it^.shares many common features, such as protein aggregation, with a broader spectrum of neutodegenerative diseases. PD can present with additional clinical impairments and dementia is common in PD patients. Despite the knowledge that the loss of specific dopaminergic neurons in the midbrain is largely responsible for most of the motor dysfunction in PD, there are significant unknown about the mechanism that lead to neuronal death. Although familial PD is relatively rate, the identification of mutation in the alpha-synuclein gene has lead to the discovery that this protein is the major component of disease-characteristic inclusions known as Lewy bodies and Lewy neurites. Alpha-synuclein is normally a soluble protein, but it can polymerize into 10-15 nm fibrils with specific biophysical properties known as "amyloid" to form pathological inclusions. Pathological inclusions such as intracellular neurofibrillarytangles and extracellular Abeta peptide deposits, which are characteristic of Alzheimer's diseasae, frequently present concomitantly with alpha-synyuclein aggregates. Indeed, apha-synuclein and tau inclusions can occur in the same cells, often intertwined. Alpha-synuclein has been shown to be able to act as an induceer of tau aggregation, and both proteins can enhance the ploymerization of each other once this process is initiated. However, the molecular mechanism and the physiological changes that lead to this process have not been elucidated. Test tube experiments and transgenic mice studies will be conducted to address these issues. Studies will be conducted to assess selective vulnerability and behavioral impairments in transgenic mice resulting from alpha-synuclein and tau interactions leading to the formation of pathological consequences. Aberrant physiological alterations,such as nitrative damage and hyperphosphorylation, may be involved in mediating alpha-synuclein and tau interactions and these mechanisms will be investigated. Transgenic mouse models of Abeta peptide deposits will also be used to assess possible pathological mechanisms by which these inclusions may promote alpha-synuclein aggregation. These findings shown provide important information on mechanisms and physiological changes that lead to the formaion of alpha-synuclein and tau inclusions, and may lead to insights in planning for effective therapeutic approaches.