Title:A Link Between Nerve Growth Factor Metabolic Deregulation and Amyloid-β-Driven Inflammation in Down Syndrome
Volume: 15
Issue: 4
Author(s): Maria Florencia Iulita, Filippo Caraci and Augusto Claudio Cuello
Affiliation:
Keywords:
Alzheimer’s disease, cholinergic neurons, Down syndrome, inflammation, metallo-proteases, nerve growth factor,
nerve growth factor metabolism.
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.
