NGF-Dependent Changes in Ubiquitin Homeostasis Trigger Early Cholinergic Degeneration in Cellular and Animal AD-Model.

ABSTRACT: Basal forebrain cholinergic neurons (BFCNs) depend on nerve growth factor (NGF) for their survival/differentiation and innervate cortical and hippocampal regions involved in memory/learning processes. Cholinergic hypofunction and/or degeneration early occurs at prodromal stages of Alzheimer's disease (AD) neuropathology in correlation with synaptic damages, cognitive decline and behavioral disability. Alteration(s) in ubiquitin-proteasome system (UPS) is also a pivotal AD hallmark but whether it plays a causative, or only a secondary role, in early synaptic failure associated with disease onset remains unclear. We previously reported that impairment of NGF/TrkA signaling pathway in cholinergic-enriched septo-hippocampal primary neurons triggers "dying-back" degenerative processes which occ

SUBMITTER: Latina V 

PROVIDER: S-EPMC6300588 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature