Inactive variants of death receptor p75NTR reduce Alzheimer's neuropathology by interfering with APP internalization

ABSTRACT: A prevalent model of Alzheimer's disease (AD) pathogenesis postulates the generation of neurotoxic fragments derived from the amyloid precursor protein (APP) after its internalization to endocytic compartments. The molecular pathways that regulate APP internalization and intracellular trafficking in neurons are incompletely understood. Here we report that 5xFAD mice, an animal model of AD, expressing signaling-deficient variants of the p75 neurotrophin receptor (p75NTR) show greater neuroprotection from AD neuropathology than animals lacking this receptor. p75NTR knock-in mice lacking the death domain or transmembrane Cys259 showed lower levels of A? species, amyloid plaque burden, gliosis, mitochondrial stress and neurite dystrophy than global knock-outs. Strikingly, long-term synaptic pl

SUBMITTER: Prof. Chenju Yi 

PROVIDER: S-SCDT-EMBOJ-2020-104450 | biostudies-other |

REPOSITORIES: biostudies-other