Lee Virginia M-Y, Giasson Benoit I, Trojanowski John Q
The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and Institute on Aging, the University of Pennsylvania, Philadelphia, PA 19104-4283, USA.
Trends Neurosci. 2004 Mar;27(3):129-34. doi: 10.1016/j.tins.2004.01.007.
Intracytoplasmic filamentous aggregates, such as neurofibrillary tangles in Alzheimer's disease and Lewy bodies in Parkinson's disease, are composed of the proteins tau and alpha-synuclein, respectively. These pathological inclusions are linked directly to the etiology and mechanisms of disease in a wide spectrum of neurodegenerative disorders, termed 'tauopathies' and 'synucleinopathies'. Emerging evidence indicates that there is frequent overlap of the pathological and clinical features of patients with tauopathies and synucleinopathies, thereby re-enforcing the notion that these disorders might be linked mechanistically. Indeed, several lines of investigation suggest that tau and alpha-synuclein might constitute a unique class of unstructured proteins that assemble predominantly into homopolymeric (rather than heteropolymeric) fibrils, which deposit mainly in separate amyloid inclusions, but occasionally deposit together. Thus, the ability of tau and alpha-synuclein to affect each other directly or indirectly might contribute to the overlap in the clinical and pathological features of tauopathies and synucleinopathies.
胞质内丝状聚集体，如阿尔茨海默病中的神经原纤维缠结和帕金森病中的路易小体，分别由蛋白质tau和α-突触核蛋白组成。这些病理性包涵体与广泛的神经退行性疾病（称为“tau蛋白病”和“突触核蛋白病”）的病因和发病机制直接相关。新出现的证据表明，tau蛋白病和突触核蛋白病患者的病理和临床特征经常重叠，从而强化了这些疾病可能在机制上存在联系的观点。事实上，多项研究表明，tau和α-突触核蛋白可能构成一类独特的无结构蛋白，它们主要组装成同聚物（而非异聚物）纤维，这些纤维主要沉积在单独的淀粉样包涵体中，但偶尔也会一起沉积。因此，tau和α-突触核蛋白直接或间接相互影响的能力可能导致tau蛋白病和突触核蛋白病在临床和病理特征上的重叠。
