title: The failure in NGF maturation and its increased degradation as the probable cause for the vulnerability of cholinergic neurons in Alzheimer's disease.
abstract: This short review discusses the arguments to consider the dismetabolism of the pathway responsible for both the maturation and degradation of NGF as the culprit of vulnerability of the forebrain cholinergic system to the Alzheimer's disease neuropathology. This summary includes information regarding a novel metabolic cascade converting Pro-NGF to mature NGF in the extracellular space and its ultimate degradation by a metalloprotease. It also describes how this pathway is altered in Alzheimer's disease with the consequential CNS accumulation of proNGF and impairment in the formation of NGF along with increased degradation of this key trophic factor. This metabolic scenario in Alzheimer's disease should result in the failure of NGF trophic support to forebrain cholinergic neurons and thus explaining the vulnerability of these neurons in this neurodegenerative condition.
authors.affiliation: Departments of Pharmacology & Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC, Canada. claudio.cuello@mcgill.ca
authors.forename: A Claudio
authors.initials: AC
authors.lastname: Cuello
authors.forename: Martin A
authors.initials: MA
authors.lastname: Bruno
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D045726:Metalloproteases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000473:pathology*; D016548:Prosencephalon / Q000473:pathology
chemical_list: D020932:Nerve Growth Factor; D045726:Metalloproteases