Nature. A new target for neurodegenerative diseases has been found: inhibiting the spread of tau.

A key feature of many neurodegenerative diseases is the slow accumulation of misfolded protein deposits in brain neurons.in particular, the accumulation and diffusion of a protein called tau is characteristic of a variety of dementia, from the most common form of dementia to chronic traumatic encephalopathy.pathological tau interacts with the normal (physiological) tau already existing in neurons, and acts as a template for misfolding of normal proteins, thus spreading tau pathology in the neural network.therefore, it is interesting to elucidate the mechanism that allows pathogenic tau to exit one neuron and enter another.on April 1, 2020, Kenneth s. Kosik team of the University of California, Santa Barbara, USA published a research paper entitled "LRP1 is a master regulator of tau uptake and spread" online in nature. The study showed that low density lipoprotein receptor associated protein 1 (LRP1) controls the endocytosis and subsequent transmission of tau.reducing LRP1 significantly reduced tau uptake in H4 glioma cells and induced pluripotent stem cell-derived neurons. The interaction between tau and LRP1 is mediated by lysine residues in the microtubule binding repeat region of tau.in addition, it was found that the down-regulation of LRP1 can effectively reduce the transmission of tau between neurons in vivo model of tau transmission.in conclusion, the results of this study confirm that LRP1 is a key regulator of tau diffusion in the brain and therefore a potential target for the treatment of diseases involving the diffusion and aggregation of tau.finally, Katrin deinhardt of the University of Southampton, UK, published a review article entitled "a receptor that lets dementia associated tau proteins into nerves" online in nature. The article systematically reviewed the research results and pointed out that this work is aimed at the first step towards the prevention of tau related diseases.in the form of tau associated dementia or traumatic encephalopathy, disease progression is associated with diffusion of tau deposits throughout the brain.it is believed that this is due to misfolded, disease-related (pathological) tau entering healthy neurons.pathological tau interacts with the normal (physiological) tau already existing in neurons, and acts as a template for misfolding of normal proteins, thus spreading tau pathology in the neural network.therefore, it is interesting to elucidate the mechanism that allows pathogenic tau to exit one neuron and enter another.this study shows that low density lipoprotein receptor associated protein 1 (LRP1) controls the endocytosis and subsequent transmission of tau. Br / >the number of neurons in HP1 < 4-induced gliomas decreased significantly. The interaction between tau and LRP1 is mediated by lysine residues in the microtubule binding repeat region of tau.in addition, it was found that the down-regulation of LRP1 can effectively reduce the transmission of tau between neurons in vivo model of tau transmission.the results of this study confirm that LRP1 is a key regulator of tau diffusion in the brain and therefore a potential target for the treatment of diseases involving the diffusion and aggregation of tau. in conclusion, LRP1 is the major regulator of tau protein endocytosis in neurons, and tau plays an important role in the transmission of tau in the brain. targeting LRP1 can significantly reduce tau diffusion in vivo, which may indicate a new treatment for tau related neurodegenerative diseases. therefore, this work has enhanced our understanding of tau transmission, emphasizing that LRP1 is a key determinant of tau transmission. reference message: