title: A Link Between Nerve Growth Factor Metabolic Deregulation and Amyloid-β-Driven Inflammation in Down Syndrome.
abstract: In Alzheimer's disease and Down syndrome, cholinergic neurons of the basal forebrain progressively degenerate. This neurotransmitter system is the main source of acetylcholine to the cortex and hippocampus. In the mature and fully differentiated central nervous system, the phenotype of forebrain cholinergic neurons and their nerve terminals in cortex and hippocampus depend on the continuous endogenous supply of nerve growth factor (NGF). It has been recently demonstrated that NGF is secreted from cortical neurons in an activity-dependent manner as a precursor molecule, proNGF. Individuals with Alzheimer's disease and Down syndrome exhibit proNGF accumulation in cortex, yet cholinergic neurons become atrophic in both diseases, despite the apparent abundance of the NGF precursor. This review illustrates the recent evidence that NGF metabolism is affected both in Alzheimer's disease and in Down syndrome brains and also discusses a role for amyloid-β peptides and central nervous system inflammation in unleashing such deficits. It further considers the potential of the NGF metabolic pathway as a new pharmacological target to slow down the neurodegenerative process both in Alzheimer's disease and in individuals with Down syndrome.
authors.forename: Maria Florencia
authors.initials: MF
authors.lastname: Iulita
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, 3655 Sir- William-Osler Promenade, Room 1210, Montreal, QC, H3G 1Y6, Canada. claudio.cuello@mcgill.ca.
authors.forename: Augusto Claudio
authors.initials: AC
authors.lastname: Cuello
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D059329:Cholinergic Neurons / Q000378:metabolism; D004314:Down Syndrome / Q000473:pathology*; D006801:Humans; D020932:Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D020932:Nerve Growth Factor