Treatment of Alzheimer's disease: from pharmacology to a better understanding of disease pathophysiology.
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.
Silvestrelli
Giorgio
G
Section of Neurology, Department of Medical and Surgical Specialisties and Public Health, University of Perugia, Ospedale Silvestrini, 06156 Perugia, Italy. silvestrelli@tin.it
Lanari
Alessia
A
Parnetti
Lucilla
L
Tomassoni
Daniele
D
Amenta
Francesco
F
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
D016229:Amyloid beta-Peptides; D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D000109:Acetylcholine