ProNGF elicits retrograde axonal degeneration of basal forebrain neurons through p75^NTR and induction of amyloid precursor protein.

ABSTRACT: Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple regions in the brain to regulate cognitive functions. Degeneration of BFCNs is seen with aging, after brain injury, and in neurodegenerative disorders. An increase in the amount of the immature proform of nerve growth factor (proNGF) in the cerebral cortex results in retrograde degeneration of BFCNs through activation of proNGF receptor p75^NTR. Here, we investigated the signaling cascades initiated at the axon terminal that mediate proNGF-induced retrograde degeneration. We found that local axonal protein synthesis and retrograde transport mediated proNGF-induced degeneration initiated from the axon terminal. Analysis of the nascent axonal proteome revealed that proNGF stimulation of axonal terminals

SUBMITTER: Dasgupta S 

PROVIDER: S-EPMC11487763 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature