Modulation of the p75 neurotrophin receptor suppresses age-related basal forebrain cholinergic neuron degeneration.

ABSTRACT: Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) is linked to cognitive impairment. The p75 neurotrophin receptor (p75^NTR) has been proposed to mediate neuronal degeneration in aging. Therefore, we tested the hypothesis that modifying p75^NTR function would prevent or reverse aging-related neuronal degeneration using LM11A-31, a small molecule p75^NTR modulator that downregulates degenerative and upregulates trophic receptor-associated signaling. Morphological analysis in mice showed loss of BFCN area detectable by 18 months of age. Oral administration of LM11A-31 from age 15 to 18 months resulted in a dose-related preservation of BFCN area and one month of treatment from 17 to 18 months also preserved cell area. To evaluate reversal of

SUBMITTER: Xie Y 

PROVIDER: S-EPMC6437186 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature