Pharmacotherapy of Alzheimer's disease: current and future trends.
Humans; Alzheimer's disease; Alzheimer Disease/*drug therapy; anti-inflammatory agents; antioxidants; cholinesterase inhibitors; dementia; Drug Therapy/*methods/*trends; immunotherapy; memantine; multi-targeted drugs; natural products; pharmacotherapy
Alzheimer's disease (AD) and its related dementia has shown an alarming rise in the global population. Although considerable efforts have been made to develop effective therapeutic agents for AD therapy, drug development has not met significant clinical success. Current pharmacotherapy of AD is limited to cholinesterase inhibitors and the N-methyl-D-aspartate antagonist memantine. Considerable research is underway to develop newer agents for the management of AD. Since amyloid-beta (Abeta) has been implicated in AD pathogenesis, the use of beta secretase inhibitors as well as immunotherapy against Abeta has been investigated. A considerable effort has been spent investigating the therapeutic potential of antioxidants and anti-inflammatory agents, several of natural products and dietary origin, in AD treatment. Numerous drug targets have also been investigated for AD treatment and a modest drug pipeline is available. Despite these efforts, drug development for AD has proved extremely difficult and most clinical trials have afforded disappointing results.
Geldenhuys Werner J; Darvesh Altaf S
Expert review of neurotherapeutics
2015
2015-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1586/14737175.2015.990884" target="_blank" rel="noreferrer noopener">10.1586/14737175.2015.990884</a>
The serotonin 5-HT6 receptor: a viable drug target for treating cognitive deficits in Alzheimer's disease.
Humans; Animals; Structure-Activity Relationship; Serotonin/*metabolism; Drug Design; Alzheimer Disease/*complications; Cognition Disorders/*drug therapy/*etiology; Serotonin Antagonists/chemistry/*therapeutic use; Receptors; Biological; Models
The serotonin 6 receptor is attracting attention as an etiological contributor in cognition deficits in diseases such as Alzheimer's disease, anxiety/depression and schizophrenia. In this review, we discuss the role of this recently discovered G protein-coupled receptor in cognition and memory, particularly in Alzheimer's disease. A surge in publications that describe the development of ligands for this receptor have recently come to light, underscoring the emerging interest in this receptor as a drug target. We also explore the current status of structure-activity relationship studies that have focused on the design of novel antagonists for the serotonin 6 receptor.
Geldenhuys Werner J; Van der Schyf Cornelis J
Expert review of neurotherapeutics
2009
2009-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1586/ern.09.51" target="_blank" rel="noreferrer noopener">10.1586/ern.09.51</a>
Oxidative stress and Alzheimer's disease: dietary polyphenols as potential therapeutic agents.
Humans; Animals; Oxidative Stress/drug effects/*physiology; Alzheimer Disease/*physiopathology/*therapy; Antioxidants/*administration & dosage/chemistry/pharmacology; Flavonoids/*administration & dosage/chemistry/pharmacology; Mitochondria/drug effects/physiology; Neurodegenerative Diseases/physiopathology; Phenols/*administration & dosage/chemistry/pharmacology; Polyphenols
Oxidative stress has been strongly implicated in the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). In recent years, antioxidants - especially those of dietary origin - have been suggested as possible agents useful for the prevention and treatment of AD. This article reviews the role of oxidative stress and the contribution of free radicals in the development of AD, and also discusses the use of antioxidants as a therapeutic strategy in the amelioration of this illness. The antioxidant potential of polyphenolic compounds obtained from dietary sources, such as anthocyanins from berries, catechins and theaflavins from tea, curcumin from turmeric, resveratrol from grapes and peanuts, the dihydrochalcones aspalathin and nothofagin from rooibos and the xanthone mangiferin from honeybush, are discussed in this review. The neuroprotective effects of these phytochemicals in preclinical models of AD are highlighted. Finally, innovative concepts, novel hypotheses, current challenges and future directions in the use of dietary polyphenols for the treatment of AD are discussed.
Darvesh Altaf S; Carroll Richard T; Bishayee Anupam; Geldenhuys Werner J; Van der Schyf Cornelis J
Expert review of neurotherapeutics
2010
2010-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1586/ern.10.42" target="_blank" rel="noreferrer noopener">10.1586/ern.10.42</a>