Curcumin Ameliorates Neuroinflammation, Neurodegeneration, and Memory Deficits in p25 Transgenic Mouse Model that Bears Hallmarks of Alzheimer’s Disease
| Autor: | Charlene Priscilla Poore, Jeyapriya R. Sundaram, Sashi Kesavapany, Wei Fun Cheong, Sally A. Frautschy, Tej K. Pareek, Markus R. Wenk, Noor Hazim Bin Sulaimee, Harish C. Pant, Chian-Ming Low |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Curcumin Amyloid Neuroimmunomodulation Anti-Inflammatory Agents Inflammation Mice Transgenic Disease Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease medicine Animals Humans Neuroinflammation Nootropic Agents Memory Disorders business.industry General Neuroscience Cyclin-dependent kinase 5 Neurodegeneration Brain General Medicine medicine.disease eye diseases Mice Inbred C57BL Psychiatry and Mental health Clinical Psychology 030104 developmental biology Neuroprotective Agents chemistry Astrocytes Nerve Degeneration Mice Inbred CBA Geriatrics and Gerontology medicine.symptom business Calcium-Calmodulin-Dependent Protein Kinase Type 2 Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | J Alzheimers Dis |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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