title: Alzheimer's disease: the pharmacological pathway.
abstract: 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.
authors.affiliation: Laboratoire de Pharmacologie Expérimentale et Clinique, Faculté de Médecine, Université de Rennes I, CS 34317, 35043 Rennes cedex, France. herve.allain@univ-rennes1.fr
authors.forename: Hervé
authors.initials: H
authors.lastname: Allain
authors.forename: Danièle
authors.initials: D
authors.lastname: Bentué-Ferrer
authors.forename: Olivier
authors.initials: O
authors.lastname: Tribut
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.forename: Bernard-François
authors.initials: BF
authors.lastname: Michel
authors.forename: Christophe
authors.initials: C
authors.lastname: Drieu-La Rochelle
mesh_terms: 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
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D004967:Estrogens; D018683:Excitatory Amino Acid Agents; D000960:Hypolipidemic Agents; D018722:Nicotinic Agonists; D020169:Caspases