The Failure in NGF Maturation and its Increased Degradation as the Probable Cause for the Vulnerability of Cholinergic Neurons in Alzheimer’s Disease
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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.
KeywordsAlzheimer’s disease Pro-NGF NGF Metalloprotease Cholinergic neurons Trophic factor Neurodegeneration
- 11.Hock C, Heese K, Hulette C, Rosenberg C, Otten U (2000) Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol 57(6):846–851PubMedCrossRefGoogle Scholar
- 17.Hock C, Maddalena A, Heuser I, Naber D, Oertel W, von der KH et al (2000) Treatment with the selective muscarinic agonist talsaclidine decreases cerebrospinal fluid levels of total amyloid beta-peptide in patients with Alzheimer’s disease. Ann NY Acad Sci 920:285–291Google Scholar
- 19.Bruno et al (2006) Alzheimer’s and Dementia. J Alzheimer’s Assoc 2(S3):S476Google Scholar