Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment due to neuronal death. Although the lost of cognitive function is the main problem for AD subjects, death occurs due to secondary issues such as concomitant infections, respiratory complications or multi-organ failure. Current drugs used in AD are acetylcholinesterase inhibitors and antagonists of the N-methyl-D-aspartate receptor. These drugs may only slightly improve cognitive functions but have only very limited impact on the clinical course of the disease. Over the last 5 years, new targets were identified and innovative drugs against AD have been designed and developed. Worthy of mention are β-secretase inhibitors, monoclonal antibodies against amyloid-β-peptide and tau inhibitors. However, although promising beneficial effects were highlighted in the data from preclinical studies, only few of these new drugs improved cognitive functions for a significant time frame in AD subjects. Controversial is the therapeutic effect on AD obtained through the manipulation of the nitric oxide synthase/nitric oxide system since the potential toxic effects on brain function could overcome the beneficial effects. The aim of this review is to analyze from a pharmacologic point of view both old and new drugs developed for the treatment of AD. In addition, the risk/benefit ratio related to the modulation of the nitric oxide synthase/nitric oxide system in AD brain will be analyzed.
Keywords: Acetylcholinesterase inhibitors, Alzhiemers disease, Amyloid β peptide, Memantine, Nitric oxide, Secretases, Tau Protein, APOE, CREB, Latrepirdine, EVT 101
CNS & Neurological Disorders - Drug Targets
Title: Experimental Research on Nitric Oxide and the Therapy of Alzheimer Disease: A Challenging Bridge
Volume: 10 Issue: 7
Author(s): Raffaella Siciliano, Eugenio Barone, Vittorio Calabrese, Vincenzo Rispoli, D. Allan Butterfield and Cesare Mancuso
Affiliation:
Keywords: Acetylcholinesterase inhibitors, Alzhiemers disease, Amyloid β peptide, Memantine, Nitric oxide, Secretases, Tau Protein, APOE, CREB, Latrepirdine, EVT 101
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment due to neuronal death. Although the lost of cognitive function is the main problem for AD subjects, death occurs due to secondary issues such as concomitant infections, respiratory complications or multi-organ failure. Current drugs used in AD are acetylcholinesterase inhibitors and antagonists of the N-methyl-D-aspartate receptor. These drugs may only slightly improve cognitive functions but have only very limited impact on the clinical course of the disease. Over the last 5 years, new targets were identified and innovative drugs against AD have been designed and developed. Worthy of mention are β-secretase inhibitors, monoclonal antibodies against amyloid-β-peptide and tau inhibitors. However, although promising beneficial effects were highlighted in the data from preclinical studies, only few of these new drugs improved cognitive functions for a significant time frame in AD subjects. Controversial is the therapeutic effect on AD obtained through the manipulation of the nitric oxide synthase/nitric oxide system since the potential toxic effects on brain function could overcome the beneficial effects. The aim of this review is to analyze from a pharmacologic point of view both old and new drugs developed for the treatment of AD. In addition, the risk/benefit ratio related to the modulation of the nitric oxide synthase/nitric oxide system in AD brain will be analyzed.
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Cite this article as:
Siciliano Raffaella, Barone Eugenio, Calabrese Vittorio, Rispoli Vincenzo, Allan Butterfield D. and Mancuso Cesare, Experimental Research on Nitric Oxide and the Therapy of Alzheimer Disease: A Challenging Bridge, CNS & Neurological Disorders - Drug Targets 2011; 10 (7) . https://dx.doi.org/10.2174/187152711798072356
DOI https://dx.doi.org/10.2174/187152711798072356 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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