Uncorrected Author Proof
Journal of Alzheimer’s Disease xx (20xx) x–xx
DOI 10.3233/JAD-170188
IOS Press
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Review 1
The Mechanisms of Action of Curcumin
in Alzheimer’s Disease
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Mengxi Tang and Changiz Taghibiglou
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Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada 5
Handling Associate Editor: Jia Liu 6
Accepted 10 April 2017
Abstract. Alzheimer’s disease (AD) is a neurodegenerative disorder of the elderly. As the prevalence of AD rises in the 21st
century, there is an urgent need for the development of effective pharmacotherapies. Currently, drug treatments target the
symptoms of the disease and do not modify or halt the disease progress. Thus, natural compounds have been investigated
for their ability to treat AD. This review examines the efficacy of curcumin, a polyphenol derived from turmeric herb,
to treat AD. We summarize the in vivo and in vitro research describing the mechanisms of action in which curcumin
modifies AD pathology: curcumin inhibits the formation and promotes the disaggregation of amyloid- plaques, attenuates
the hyperphosphorylation of tau and enhances its clearance, binds copper, lowers cholesterol, modifies microglial activity,
inhibits acetylcholinesterase, mediates the insulin signaling pathway, and is an antioxidant. In conclusion, curcumin has the
potential to be more efficacious than current treatments. However, its usefulness as a therapeutic agent may be hindered by
its low bioavailability. If the challenge of low bioavailability is overcome, curcumin-based medications for AD may be in the
horizon.
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Keywords: Alzheimer’s disease, amyloid, curcumin, turmeric, tau protein 18
INTRODUCTION 19
Alzheimer’s disease (AD), accounting for 60 to 20
80% of dementia cases, is an irreversible, pro- 21
gressive brain disorder characterized by behavioral 22
changes and loss of cognitive functions [1]. Common 23
symptoms include short-term memory loss, cogni- 24
tive deficits, and an inability to perform tasks of 25
daily living [2]. As the disease progresses, afflicted 26
individuals often withdraw from society, lose bod- 27
ily functions, and die. The life expectancy following 28
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Correspondence to: Changiz Taghibiglou, PharmD/PhD,
Associate Professor, Department of Pharmacology, College
of Medicine, University of Saskatchewan, 107 Wiggins Road,
Saskatoon, SK, S7N 5E5, Canada. Tel.: +1 306 966 8816; E-mail:
changiz.taghibiglou@usask.ca.
diagnosis ranges from an average of three to nine 29
years [3]. Globally, approximately 46 million people 30
are afflicted with dementia and the population ages, 31
the number is projected to increase to 131.5 million 32
by 2050 [4]. The worldwide cost of dementia is US 33
$818 billion and is expected to be a trillion dollar 34
disease in 2018 [4]. Given the economic cost and the 35
increasing prevalence of the disease, it is essential to 36
explore drug therapies. 37
Presently, there are a limited number of synthetic 38
drugs that are available for the management of the 39
disease. However, several natural compounds have 40
been investigated for their efficacy in treating AD 41
[5]. Curcumin is a natural compound derived from 42
the herb turmeric [6]. Recent research has focused on 43
its mechanisms of action by which it can modulate 44
AD progression.
ISSN 1387-2877/17/$35.00 © 2017 – IOS Press and the authors. All rights reserved