Please use this identifier to cite or link to this item: https://doi.org/10.3233/JAD-170093
Title: Curcumin Ameliorates Neuroinflammation, Neurodegeneration, and Memory Deficits in p25 Transgenic Mouse Model that Bears Hallmarks of Alzheimer's Disease
Authors: Sundaram, Jeyapriya Raja
Poore, Charlene Priscilla
Bin Sulaimee, Noor Hazim
Pareek, Tej
Cheong, Wei Fun 
Wenk, Markus R 
Pant, Harish C
Frautschy, Sally A
Low, Chian-Ming 
Kesavapany, Sashi
Keywords: Science & Technology
Life Sciences & Biomedicine
Neurosciences
Neurosciences & Neurology
Amyloid
Cdk5
curcumin
neurodegeneration
neuroinflammation
p25
tau
CYCLIN-DEPENDENT KINASE-5
CDK5 INHIBITORY PEPTIDE
A-BETA
IN-VIVO
PLAQUE-FORMATION
COGNITIVE DEFICITS
AMYLOID PATHOLOGY
PRECURSOR PROTEIN
SILVER STAIN
NEURON LOSS
Issue Date: 1-Jan-2017
Publisher: IOS PRESS
Citation: Sundaram, Jeyapriya Raja, Poore, Charlene Priscilla, Bin Sulaimee, Noor Hazim, Pareek, Tej, Cheong, Wei Fun, Wenk, Markus R, Pant, Harish C, Frautschy, Sally A, Low, Chian-Ming, Kesavapany, Sashi (2017-01-01). Curcumin Ameliorates Neuroinflammation, Neurodegeneration, and Memory Deficits in p25 Transgenic Mouse Model that Bears Hallmarks of Alzheimer's Disease. JOURNAL OF ALZHEIMERS DISEASE 60 (4) : 1429-1442. ScholarBank@NUS Repository. https://doi.org/10.3233/JAD-170093
Abstract: Several studies have indicated that neuroinflammation is indeed associated with neurodegenerative disease pathology. However, failures of recent clinical trials of anti-inflammatory agents in neurodegenerative disorders have emphasized the need to better understand the complexity of the neuroinflammatory process in order to unravel its link with neurodegeneration. Deregulation of Cyclin-dependent kinase 5 (Cdk5) activity by production of its hyperactivator p25 is involved in the formation of tau and amyloid pathology reminiscent of Alzheimer's disease (AD). Recent studies show an association between p25/Cdk5 hyperactivation and robust neuroinflammation. In addition, we recently reported the novel link between the p25/Cdk5 hyperactivation-induced inflammatory responses and neurodegenerative changes using a transgenic mouse that overexpresses p25 (p25Tg). In this study, we aimed to understand the effects of early intervention with a potent natural anti-inflammatory agent, curcumin, on p25-mediated neuroinflammation and the progression of neurodegeneration in p25Tg mice. The results from this study showed that curcumin effectively counteracted the p25-mediated glial activation and pro-inflammatory chemokines/cytokines production in p25Tg mice. Moreover, this curcumin-mediated suppression of neuroinflammation reduced the progression of p25-induced tau/amyloid pathology and in turn ameliorated the p25-induced cognitive impairments. It is widely acknowledged that to treat AD, one must target the early-stage of pathological changes to protect neurons from irreversible damage. In line with this, our results demonstrated that early intervention of inflammation could reduce the progression of AD-like pathological outcomes. Moreover, our data provide a rationale for the potential use of curcuminoids in the treatment of inflammation associated neurodegenerative diseases.
Source Title: JOURNAL OF ALZHEIMERS DISEASE
URI: https://scholarbank.nus.edu.sg/handle/10635/173276
ISSN: 13872877
18758908
DOI: 10.3233/JAD-170093
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