title: Gangliosides, NGF, brain aging and disease: a mini-review with personal reflections.
abstract: In this mini-review I summarize our research efforts in ascertaining the possible neuro-reparative properties of the GM1 ganglioside and its cooperative effects with NGF in stroke-lesion models. We also review aspects of our NGF investigations which have recently led to the discovery that NGF is released in an activity-dependent manner in the form of its precursor molecule, proNGF. These studies support the notion that in the CNS NGF metabolism conversion and degradation occur in the extracellular milieu. We have also validated this pathway in vivo demonstrating that the pharmacological inhibition of the pro-to mature NGF conversion results in the brain accumulation of proNGF and loss and atrophy of cortical cholinergic synapses. Furthermore, we have gathered neurochemical evidence for a compromise of this newly discovered NGF metabolic pathway in Alzheimer's disease, explaining the vulnerability of NGF-dependent forebrain cholinergic neurons in this disease despite normal NGF synthesis and abundance of NGF precursor.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada. Claudio.cuello@mcgill.ca
authors.forename: A Claudio
authors.initials: AC
authors.lastname: Cuello
mesh_terms: D000375:Aging; D000818:Animals; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000502:physiology*; D059329:Cholinergic Neurons / Q000502:physiology*; D005677:G(M1) Ganglioside / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000627:therapeutic use; D011498:Protein Precursors / Q000378:metabolism* / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D011498:Protein Precursors; C061397:pro-nerve growth factor, human; D005677:G(M1) Ganglioside; D020932:Nerve Growth Factor; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9