Molecular rationale for the pharmacological treatment of Alzheimer's disease

Drugs & Aging
Martina ZimmermannMonica Di Luca

Abstract

Cerebral deposition of amyloid plaques containing amyloid beta-peptide (Abeta) has traditionally been considered the central feature of Alzheimer's disease (AD). Abeta is derived from amyloid precursor protein (APP), which is cleaved by several different proteases: alpha-, beta- and gamma-secretase. In the past decade, however, the molecular pathogenesis of AD has been shown to involve alterations in several neurotransmitter, inflammatory, oxidative, and hormonal pathways that represent potential targets for AD prevention and treatment. Much research has shown a direct link between cholinergic impairment and altered APP processing as a major pathogenetic event in AD. Three highly probable mechanisms of APP regulation through inhibition of acetylcholinesterase are thus current topics of investigation. Indeed, acetylcholinesterase inhibitors appear to cause selective muscarinic activation of alpha-secretase and to induce the translation of APP mRNA; they may also restrict amyloid fibre assembly. Activation of N-methyl-D-aspartate receptors is considered a probable cause of chronic neurodegeneration in AD, and memantine has been widely used in some countries in AD patients to block cerebral N-methyl-D-aspartate receptors that norm...Continue Reading

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Citations

Dec 22, 2010·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Martina Zimmermann
May 29, 2010·Genome Biology·Mohammad Ali FaghihiClaes Wahlestedt
Jun 2, 2009·Current Opinion in Immunology·Rakez Kayed, George R Jackson
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Aug 25, 2007·Pharmacology & Therapeutics·Mark A Findeis
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Mar 3, 2012·Advances in Physiology Education·Ute BurkhardtMartina Zimmermann

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