Nerve growth factor pharmacology: application to the treatment of cholinergic neurodegeneration in Alzheimer's disease.
The proposal that NGF or compounds that induce the expression of endogenous NGF may be useful in the treatment of AD is based upon a wealth of evidence showing that NGF effectively attenuates lesion-induced cholinergic deficits and cognitive impairments in animal models. In addition, a recent clinical study with chronic NGF treatment in an AD patient showed promise. Olson et al. showed that NGF treatment increased blood flow, [11C]nicotine uptake, and 11C binding in the cerebral cortex. In addition, NGF infusions normalized EEG patterns and improved performance in word recognition tests. Further clinical trials with either NGF or NGF-enhancing compounds will allow determination of whether the animal-based study approach to designing clinically relevant drugs will be advantageous to the treatment of AD. Further findings on the effectiveness of NGF in AD patients are reported by Lars Olson (this volume).
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D000109:Acetylcholine / Q000502:physiology*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009410:Nerve Degeneration / Q000187:drug effects / Q000502:physiology*; D009414:Nerve Growth Factors / Q000502:physiology* / Q000627:therapeutic use*; D009474:Neurons / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020917:Receptor, trkA; D011976:Receptors, Muscarinic / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013569:Synapses / Q000502:physiology
D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D011976:Receptors, Muscarinic; D017475:Receptors, Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D000109:Acetylcholine