Neurochemical Research

, Volume 32, Issue 6, pp 1041–1045

The Failure in NGF Maturation and its Increased Degradation as the Probable Cause for the Vulnerability of Cholinergic Neurons in Alzheimer’s Disease

Original Paper

DOI: 10.1007/s11064-006-9270-0

Cite this article as:
Cuello, A.C. & Bruno, M.A. Neurochem Res (2007) 32: 1041. doi:10.1007/s11064-006-9270-0

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.

Keywords

Alzheimer’s diseasePro-NGFNGFMetalloproteaseCholinergic neuronsTrophic factorNeurodegeneration

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Departments of Pharmacology & TherapeuticsMcGill UniversityMontrealCanada
  2. 2.Anatomy and Cell BiologyMcGill UniversityMontrealCanada
  3. 3.Neurology and NeurosurgeryMcGill UniversityMontrealCanada