A link between nerve growth factor metabolic deregulation and amyloid-β-driven inflammation in down syndrome

Maria Florencia Iulita, Filippo Caraci, Augusto Claudio Cuello

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)434-447
Number of pages14
JournalCNS and Neurological Disorders - Drug Targets
Volume15
Issue number4
Publication statusPublished - May 1 2016

Fingerprint

Nerve Growth Factor
Down Syndrome
Amyloid
Alzheimer Disease
Inflammation
Cholinergic Neurons
Hippocampus
Central Nervous System
Prosencephalon
Metabolic Networks and Pathways
Acetylcholine
Neurotransmitter Agents
Pharmacology
Phenotype
Neurons
Peptides
Brain

Keywords

  • Alzheimer’s disease
  • Cholinergic neurons
  • Down syndrome
  • Inflammation
  • Metallo-proteases
  • Nerve growth factor
  • Nerve growth factor metabolism

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

Cite this

A link between nerve growth factor metabolic deregulation and amyloid-β-driven inflammation in down syndrome. / Iulita, Maria Florencia; Caraci, Filippo; Cuello, Augusto Claudio.

In: CNS and Neurological Disorders - Drug Targets, Vol. 15, No. 4, 01.05.2016, p. 434-447.

Research output: Contribution to journalArticle

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