JBC . . . The Li Dan team at Shanghai Jiaotong University has revealed the molecular mechanism of the disease-causing amyloid aggregation of alpha-syn and Tau of Alzheimer's disease.

Amyloid aggregation of proteins is an important pathological feature of many neurodegenerative diseases [1], such as amyloid plaques formed by a β protein in Alzheimer's disease (AD), and neurofibrillary tangles formed by tau protein in AD and other tau protein lesions [2, 3] In Parkinson's disease (PD) and other synuclein lesions, the formation of Lewy body aggregation of α - synuclein (α - SYN) proteins and so on [4,5]. Elucidating the amyloid aggregation mechanism of these pathogenic proteins has important guiding significance for drug research and development of related diseases.there are extensive overlapping clinical case features between different neurodegenerative diseases [6,7], for example, the copolymer of α - syn and tau protein was found in some ad and PD patients [8,9].this indicates that the two different pathogenic proteins may interact with each other in the corresponding diseases.it is very important to clarify the interaction between them and their CO concentration mechanism in order to explain the pathogenesis of corresponding diseases, disease diagnosis and drug development.recently, the research group of Li Dan from Bio-X Research Institute of Shanghai Jiaotong University and Liu Cong of Shanghai Institute of organic chemistry published an article entitled "structural basis of the interval between α - synuclein and tau in regulating pathway amyloid aggregation" in Journal of Biological Chemistry.this study systematically studied the interaction between α - syn and tau protein and the structural basis and mechanism of coaggregation, which is of great significance for the study of pathogenesis of related diseases.in this study, we found that in addition to forming pathogenic amyloid fibers, α - syn and tau can interact directly and promote the co aggregation of the two proteins.further studies on the tht fluorescence kinetics and negative staining electron microscopy of the mutant protein by liquid phase nuclear magnetic resonance spectroscopy showed that α - syn could recognize and bind to the microtubule binding domain of tau through its C-terminal, thus promoting the formation of Tau pathological amyloid fibrillation.and the s129 phosphorylation of α - syn C-terminal, which is related to the pathology of PD, greatly enhanced the amyloid aggregation of tau protein.at the same time, tau exposed the core area of α - syn by binding to the C-terminal of α - syn, which greatly promoted the pathological aggregation of α - syn.α - syn and tau promote the aggregation of amyloid protein, and the identification of the interaction interface between α - syn and tau protein. In conclusion, this study elucidates the molecular mechanism of cross talk of key pathogenic proteins tau and α - syn in case conditions.it was found that the two promote each other's pathogenic amyloid aggregation through direct interaction.more importantly, we found that pathological phosphorylation plays an important role in this process.this study provides a new way to explain and understand the internal relationship between different neurodegenerative diseases, especially Parkinson's disease and Alzheimer's disease.Lu Jinxia of Shanghai Jiaotong University, Dr. Zhang Shengnan and Dr. Ma Xiaojuan of Shanghai Institute of organic sciences are the co first authors, and Professor Li Dan of Shanghai Jiaotong University is the corresponding author.the research work is supported by the national key basic R & D projects, the National Natural Science Foundation of China and the foundation of Shanghai Science and Technology Commission.links: 1. Eisenberg D & amp; Jucker m (2012) the amyloid state of proteins in human diseases. Cell 148 (6): 1188-1203.2, Wilcock GK & amp; esiri mm (1982) plaques, tangles and dementia. A quantitative study. J Neurol SCI 56 (2-3): 343-356.3, Lee VM, goedert m, & amp; Trojanowski JQ (2001) Neurodegenerative tauopathies. Annu Rev Neurosci 24:1121-1159.4、Crowther RA, Daniel SE, & Goedert M (2000) Characterisation of isolated alpha-synuclein filaments from substantia nigra of Parkinson's disease brain. Neurosci Lett 292(2):128-130.5、Goedert M, Spillantini MG, Del Tredici K, & Braak H (2013) 100 years of Lewy pathology. Nat Rev Neurol 9(1):13-24.6、 Hansen L, et al. (1990) The Lewy body variant of Alzheimer's disease: a clinical and pathologic entity. Neurology 40(1):1-8.7、Moussaud S, et al. (2014) Alpha-synuclein and tau: teammates in neurodegeneration? Mol Neurodegener 9:43.8、Giasson BI, et al. (2003) Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 300(5619):636-640.9、Colom-Cadena M, et al. (2013) Confluence of alpha-synuclein, tau, and beta-amyloid pathologies in dementia with Lewy bodies. J Neuropathol Exp Neurol 72(12):1203-1212.