Cholinergic nicotinic systems in Alzheimer's disease: prospects for pharmacological intervention.
Within the last few years, research into the cause and progression of Alzheimer's disease has made significant advances. Although there is still no preventative treatment or cure for this neurodegenerative illness, the development of drugs that may alleviate some of the cognitive symptoms associated with it is advancing. Cholinesterase inhibitors are at present the most effective form of treatment and have shown significant overall response rates in clinical trials. However, although some patients show substantial improvement when treated with this class of drugs, there is considerable variability in the amount of benefit gained in different individuals in terms of their cognitive and behavioural functioning. Furthermore, unfortunately some patients gain little or no benefit from these drugs. It would therefore be of great advantage to explore alternative therapeutic possibilities. This article reviews the potential involvement of the nicotinic cholinergic system in Alzheimer's disease and discusses the possibility of nicotinic pharmacotherapy. Substantial evidence indicates the involvement of the nicotinic cholinergic system in the pathology of Alzheimer's disease. Drugs targeting these sites may not only have a positive effect on cognitive function, but also have additional therapeutic benefits in terms of restoring the hypoactivity in the excitatory amino acid pyramidal system and even slowing the emergence of Alzheimer's disease pathology. The conclusion of this review is that nicotinic treatments are an important potential source of new therapeutic interventions in Alzheimer's disease.
Vesey
Robyn
R
Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
Birrell
Jennifer M
JM
Bolton
Clare
C
Chipperfield
Ruth S
RS
Blackwell
Andrew D
AD
Dening
Tom R
TR
Sahakian
Barbara J
BJ
D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology* / Q000523:psychology; D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism
D018678:Cholinergic Agents; D011978:Receptors, Nicotinic; D018698:Glutamic Acid; D000109:Acetylcholine