title: Treatment of Alzheimer's disease: from pharmacology to a better understanding of disease pathophysiology.
abstract: Alzheimer's disease (AD) is the most common cause of cognitive impairment in older patients and is expected to increase greatly in prevalence in the next future. It is characterized by the development of senile plaques and neurofibrillary tangles, which are associated with neuronal loss affecting to a greater extent cholinergic neurons. A cascade of pathophysiological events is triggered in AD that ultimately involves common cellular signalling pathways and leads to cellular and neural networks dysfunction, failure of neurotransmission, cell death and a common clinical outcome. The process is asynchronous and viable neurons remain an important target for therapeutic intervention at each stage of disease evolution. At present symptomatic drugs inhibiting the degradation of acetylcholine within synapses and more recently glutamate receptor antagonists represent the mainstay of therapy. However, interventions able to halt or slow disease progression (i.e., disease-modifying agents) are necessary. Although much progress has been made in this area, there are currently no clinically approved interventions for AD classed as disease modifying or neuroprotective. This paper reviews the main symptomatic strategies available for treating AD and future strategies for improving our therapeutic approach to AD.
authors.affiliation: Section of Neurology, Department of Medical and Surgical Specialisties and Public Health, University of Perugia, Ospedale Silvestrini, 06156 Perugia, Italy. silvestrelli@tin.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Silvestrelli
authors.forename: Alessia
authors.initials: A
authors.lastname: Lanari
authors.forename: Lucilla
authors.initials: L
authors.lastname: Parnetti
authors.forename: Daniele
authors.initials: D
authors.lastname: Tomassoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Amenta
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D015195:Drug Design; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D000109:Acetylcholine