Alzheimer's disease: the pharmacological pathway.
The current pharmacological treatment of Alzheimer's disease (AD) comes down to four marketed drugs (tacrine, donepezil, rivastigmine and galantamine) all of which are cholinesterase inhibitors, conforming to the cholinergic hypothesis. The future is clearly directed at new biological targets closely linked to the pathophysiology of the disease and more precisely, the pathological hallmark of AD which includes widespread neuronal degeneration, neuritic plaques containing beta-amyloid and tau-rich neurofibrillary tangles. For clinicians, this means that new curative drugs will have to be prescribed early in the course of the disease. This review describes the main entry pathways for drug discovery in AD: (1) supplementation therapy, (2) anti-apoptotic compounds, (3) substances with a mitochondrial impact, (4) anti-amyloid substances, (5) anti-protein aggregation and (6) lipid-lowering drugs. The rapidity at which these compounds will be at our disposal is highly dependent on the policy of the pharmaceutical companies.
Allain
Hervé
H
Laboratoire de Pharmacologie Expérimentale et Clinique, Faculté de Médecine, Université de Rennes I, CS 34317, 35043 Rennes cedex, France. herve.allain@univ-rennes1.fr
Bentué-Ferrer
Danièle
D
Tribut
Olivier
O
Gauthier
Serge
S
Michel
Bernard-François
BF
Drieu-La Rochelle
Christophe
C
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004967:Estrogens / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D004967:Estrogens; D018683:Excitatory Amino Acid Agents; D000960:Hypolipidemic Agents; D018722:Nicotinic Agonists; D020169:Caspases