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How Does Turmeric Help Fight Alzheimer’s Disease? Scientists Answer in New Study
  • 작성일2022-01-28
  • 최종수정일2022-01-28
  • 담당부서연구기획과
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14th January 2022


How Does Turmeric Help Fight Alzheimer’s Disease? Scientists Answer in New Study

A novel study demonstrates how curcumin present in turmeric rhizomes exerts its neuroprotective effects.


Curcumin, a chemical compound extracted from turmeric, is known to activate Nrf2, a factor which protects nerve cells from oxidative stress, while also reducing the risk of developing Alzheimer’s disease. However, the exact mechanism by which curcumin activates Nrf2 was unknown. Scientists from Korea National Institute of Health have now revealed how this happens, providing impetus for the development of therapeutic drugs to treat Alzheimer's Disease. 


 A novel study reveals how curcumin exerts its neuroprotective effect, opening up possibilities in the development of therapeutics for Alzheimer’s disease.


It is an image that symbolizes cognitive disorders such as Alzheimer's disease. An older man is in deep thought with one hand on his forehead and the back of his head is broken and flying.

Photo courtesy: Shutterstock


Alzheimer’s disease (AD) has garnered considerable attention in the neuroscience research field, given its debilitating symptoms and the difficulty in finding a cure for it. While various treatments have been proposed for AD, a definitive solution has remained out of reach for science. Scientists now suggest that the answer may have been hiding all along in the humble turmeric spice.


Curcumin, a chemical present in turmeric, has excellent antioxidant, anti-inflammatory, antibacterial, and antitumor activities. It has also proved to be “neuroprotective” in models of neurological disorders such as stroke and traumatic brain injury. Studies in the last decade have shown that curcumin can impact various molecules and “cell signaling” pathways, including the nuclear factor erythroid-2 related factor 2 (or Nrf2) pathway.


Nrf2, normally present in mammalian cells, plays a crucial role in neuroprotection by counteracting oxidative stress and brain edema. It also helps clear the accumulation of phosphorylated tau in the brain, which is one of the main causes of AD. However, the exact mechanism by which curcumin activates Nrf2 remained elusive. That is, until now.


In a study now published in Scientific Reports, a group of scientists from Korea National Institute of Health, led by Dr. Chulman Jo, have proposed a novel, non-canonical mechanism by which curcumin activates Nrf2. They treated nerve cells with curcumin for 12 hours and observed higher levels of Nrf2 protein in the nuclei of treated cells, compared to the non-treated ones. This study was supported by a fund (4845-302-210-13) by Research of Korea Disease Control and Prevention Agency.


To further investigate whether Nrf2 activation is dependent on p62—a protein involved in programmed cell death and the removal of damaged organelles—the researchers treated mouse embryonic fibroblast cells that have p62 ‘knocked out’ (meaning that p62 is not present) with curcumin. “We observed that the phosphorylation, that is, the addition of a phosphate group, of p62 at the amino acid sequence ser351 was significantly enhanced in cells treated with curcumin,” Dr. Jo says.


The most significant result was yet to follow; they noticed that PKCδ, an enzyme that adds phosphates to other molecules, was involved in curcumin-induced phosphorylation of p62 at ser351. This was evidenced by the fact that p62-phosphorylation was enhanced in cells where PKCδ expression was increased and inhibited in those where its expression was reduced.


Drawing insights from all these experiments, the scientists concluded that curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at ser351, and, for the first time, explained the precise biological activity of curcumin in neuronal cells. 

“To the best of my knowledge, until now, nine human trials of curcumin in AD interventions have been performed or are under way,” elaborates Dr. Jo, “But none of these have explained why or how exactly curcumin acts.”


So, what are the real-life applications of this research? These findings could improve the understanding of curcumin’s neuroprotective mechanism and give scientific clues for developing therapeutic drugs for AD.


Indeed, their findings provide an interesting basis for future research and drug development for AD!


Reference

Authors

Title of original paper

Journal

JeeYun Park, HeeYoung Sohn, Young Ho Koh & Chulman Jo

Curcumin activates Nrf2 through PKCδmediated p62 phosphorylation at Ser351

Scientific Reports

DOI

Affiliations

10.1038/s41598-021-87225-8

Division of Brain Disease Research, Department for Chronic Disease Convergence Research, Korea National Institute of Health


About National Institute of Health in Korea 

The Korea National Institute of Health (KNIH), one of the major operating components of the Ministry of Health and Welfare, leads the nation’s medical research. Over the past seven decades, the KNIH has made unwavering efforts to enhance the public’s health and innovate biomedical research. The KNIH seeks to eradicate diseases and make people healthier. The KNIH establishes a scientific basis and evidence underlying health policy as well as provides national research infrastructures. We also promote public health research. To this end, we make efforts to enrich a health research environment by granting funds to research projects and keeping our resources, data, and facilities more open and accessible to researchers.

Website: http://www.nih.go.kr/NIH_ENG/


About Dr. Chulman Jo

Dr. Chulman Jo is a senior staff scientist in Division of Brain Disease Research at Korea National Institute of Health. His group is currently researching the molecular risk factors for tau pathology in Alzheimer’s disease. He completed his postdoctoral training from Gail Johnson’s lab at the Rochester University Medical Center, New York, USA. To date, he has 40 publications to his name.

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