A novel prolyl endopeptidase inhibitor, JTP-4819--its behavioral and neurochemical properties for the treatment of Alzheimer's disease.
Formation of beta-amyloid and neurofibrillary tangles in the brain due to genetic or other factors is the most frequent cause of Alzheimer's disease. In addition, marked reduction of certain brain neuropeptide levels is a consistent finding in patients with Alzheimer's disease, together with the deterioration of cholinergic neurons. Currently, there is great demand for the development of new drugs to improve memory deficits or to delay the neurodegenerative process in conditions such as Alzheimer's disease. In this report, the pharmacological actions of JTP-4819, a novel specific prolyl endopeptidase (PEP) inhibitor devised for the treatment of Alzheimer's disease, are reviewed with respect to its effects on PEP activity, neuropeptidergic and cholinergic neurons, and memory-related behavior in rats. We also discuss the possible beneficial effect of JTP-4819 on beta-amyloid metabolism and its potential neuroprotective properties.
Toide
K
K
Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka.
Shinoda
M
M
Miyazaki
A
A
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D000818:Animals; D000085822:Prolyl Oligopeptidases; D011759:Pyrrolidines / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use*
D011759:Pyrrolidines; D015842:Serine Proteinase Inhibitors; C094211:JTP 4819; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases