Biochemical models for cognition enhancers.
Although the etiology of Alzheimer's disease includes a wide range of dysfunction, the most essential dysfunction is probably in the mesolimbic acetylcholine (ACh) system. Three novel approaches to modulating ACh function were considered, somatostatin, serotonin (5-HT) and modulation of cortical ACh tone through angiotension II. Concerning somatostatin there is no correlation between the decrease in somatostatin binding sites in brain and choline-acetyl-transferase activity suggesting that modulating somatostatin is not a promising therapeutic approach to Alzheimer's disease. With 5-HT, evidence suggests that 5-HT receptors (in particular 5HT1A) are located on cholinergic projections and behavioral evidence suggests 5-HT modulation of memory function. This area could therefore develop rapidly, particularly in view of the recent discovery of numerous subtypes of 5-HT receptor. Concerning the third approach, recent evidence has shown that angiotensin converting enzyme (ACE) inhibitors can facilitate ACh release and also possess cognition enhancing activity. The possibility was also evoked that drugs such as piracetam might prevent age-related decreases in ACh receptor density. Concerning trophic factors (e.g. glutamate-induced neuronal sprouting) most approaches have induced amnesia but the search for partial glutamate agonists may have potential. Finally, a neuronal transplant approach was considered but was thought to be very difficult in view of the global brain shrinkage associated with aging and Alzheimer's disease.
Costall
B
B
Neuropharmacology Research Group, University of Bradford, England.
Barnes
J M
JM
Hamon
M
M
Müller
W E
WE
Briley
M
M
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003071:Cognition / Q000502:physiology*; D006801:Humans