Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

Xu ChenYaqiao LiChao WangYinyan TangSue-Ann MokRichard M TsaiJulio C RojasAnna KarydasBruce L MillerAdam L BoxerJason E GestwickiMichelle ArkinAna Maria CuervoLi Gan

Published in: Molecular neurodegeneration (2020)

We report that p300/CBP, a lysine acetyltransferase aberrantly activated in tauopathies, causes impairment in ALP, leading to excess tau secretion. This effect, together with increased intracellular tau accumulation, contributes to enhanced spreading of tau. Our findings suggest that inhibition of p300/CBP as a novel approach to correct ALP dysfunction and block disease progression in tauopathy.

Keyphrases

cerebrospinal fluid
oxidative stress
cell death
signaling pathway
reactive oxygen species