Open AccessCurcumin Ameliorates Neuroinflammation, Neurodegeneration, and Memory Deficits in p25 Transgenic Mouse Model that Bears Hallmarks of Alzheimer’s Disease
Author(s) -
Jeyapriya Raja Sundaram,
Charlene Priscilla Poore,
Noor Hazim Bin Sulaimee,
Tej K. Pareek,
Wei Fun Cheong,
Markus R. Wenk,
Harish C. Pant,
Sally A. Frautschy,
Chian-Ming Low,
Sashi Kesavapany
Publication year - 2017
Publication title -
journal of alzheimer's disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.677
H-Index - 139
eISSN - 1875-8908
pISSN - 1387-2877
DOI - 10.3233/jad-170093
Subject(s) - neuroinflammation , neurodegeneration , neuroscience , curcumin , inflammation , proinflammatory cytokine , alzheimer's disease , cyclin dependent kinase 5 , microglia , medicine , biology , disease , pharmacology , immunology , kinase , pathology , microbiology and biotechnology , protein kinase a , mitogen activated protein kinase kinase
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.