Trojanowski J Q, Schmidt M L, Shin R W, Bramblett G T, Rao D, Lee V M
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104-4283.
Brain Pathol. 1993 Jan;3(1):45-54. doi: 10.1111/j.1750-3639.1993.tb00725.x.
The neuronal cytoskeleton is one of the most profoundly altered organelles in late life neuro-degenerative disorders that are characterized by progressive impairments in cognitive abilities. The elucidation of the protein building blocks of these organelles as well as advances in understanding how these proteins become altered in Alzheimer's disease (AD) and other less common dementing illnesses, i.e., diffuse Lewy body disease (DLBD) or the Lewy body variant of AD (LBVAD), will provide insights into the molecular basis of these disorders. Within, we review evidence that normal adult human tau is abnormally phosphorylated and converted into the subunits of AD paired helical filaments (PHFs), and that Lewy bodies (LBs) represent accumulation of altered neurofilament (NF) triplet subunits. Although the precise biological consequences of PHF and LB formation in neurons is unknown, growing evidence suggests that the formation of PHFs and LBs from normal neuronal cytoskeletal proteins could have deleterious effects on neuronal function and survival. Finally, insights into the composition of PHFs and LBs could lead to the development of novel strategies for the timely and accurate diagnosis of AD, DLBD and the LBVAD.
神经元细胞骨架是晚年神经退行性疾病中变化最为显著的细胞器之一，这些疾病的特征是认知能力逐渐受损。阐明这些细胞器的蛋白质组成成分，以及在理解这些蛋白质在阿尔茨海默病（AD）和其他不太常见的痴呆性疾病（即弥漫性路易体病（DLBD）或AD的路易体变异型（LBVAD））中如何发生改变方面取得的进展，将为这些疾病的分子基础提供深入见解。在此，我们综述相关证据，即正常成人的tau蛋白会异常磷酸化并转化为AD双螺旋丝（PHF）的亚基，并且路易体（LB）代表了改变的神经丝（NF）三联体亚基的积累。尽管神经元中PHF和LB形成的确切生物学后果尚不清楚，但越来越多的证据表明，由正常神经元细胞骨架蛋白形成PHF和LB可能对神经元功能和存活产生有害影响。最后，对PHF和LB组成的深入了解可能会促成新策略的开发，用于及时、准确地诊断AD, DLBD和LBVAD。
