Small molecule p75NTR ligands reduce pathological phosphorylation and misfolding of tau, inflammatory changes, cholinergic degeneration, and cognitive deficits in AβPP(L/S) transgenic mice.

ABSTRACT: The p75 neurotrophin receptor (p75NTR) is involved in degenerative mechanisms related to Alzheimer's disease (AD). In addition, p75NTR levels are increased in AD and the receptor is expressed by neurons that are particularly vulnerable in the disease. Therefore, modulating p75NTR function may be a significant disease-modifying treatment approach. Prior studies indicated that the non-peptide, small molecule p75NTR ligands LM11A-31, and chemically unrelated LM11A-24, could block amyloid-β-induced deleterious signaling and neurodegeneration in vitro, and LM11A-31 was found to mitigate neuritic degeneration and behavioral deficits in a mouse model of AD. In this study, we determined whether these in vivo findings represent class effects of p75NTR ligands by examining LM11A-24 effects. In addit

SUBMITTER: Nguyen TV 

PROVIDER: S-EPMC4278429 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature