Institute of Biological Chemistry, Academia Sinica

Dr. Rita P.-Y. Chen and her research team at the Institute of Biological Chemistry has recently discovered that polyhydroxycurcuminoids, but not curcumin itself, may be useful in the prevention of Alzheimer’s disease. They found that these compounds upregulate neprilysin (NEP), the most important amyloid-β peptide (Aβ)-degrading enzyme. Many recent reports have shown that Aβ clearance is a promising strategy in preventing and treating Alzheimer’s disease, and NEP is the most important Aβ-degrading enzyme. Upregulating NEP is expected to decrease Aβ levels in affected brains, thus decreasing the risk of Alzheimer’s disease progression. The research was published in Scientific Reports, a scientific journal published by the Nature Publishing Group, on July 13th, 2016.

Diagnosis of Alzheimer’s disease is on the rise, due in part to aging populations. After diagnosis, the average life expectancy ranges from 4 to 20 years, resulting in significant economic and social burdens in medical and non-medical care.

Alzheimer’s disease is characterized by neurofibrillary tangles and senile plaques in the brain. These senile plaques are formed from Aβ peptides, which are produced in the brain during protein catabolism. Under normal conditions, NEP and several other enzymes can degrade Aβ. However, if the rate of Aβ production exceeds the rate of Aβ degradation, Aβ can accumulate in the brain and form amyloid plaques, leading to neuronal death. High plaque density regions (e.g., the hippocampus and cerebral cortex) of human Alzheimer’s brains show significantly less NEP expression. Furthermore, the expression of NEP decreases with age, which suggests that there is a strong link between NEP activity and amyloid accumulation in the brains of Alzheimer’s disease patients. It has also been reported that cognitive impairments and abnormal Aβ accumulation in the brains of transgenic Alzheimer’s disease mice can be restored by injecting stem cells or viruses that express foreign NEP.

There is low incidence of Alzheimer’s disease in the Indian population, perhaps stemming from widespread turmeric use in the diet. Curcumin is the major component of turmeric but has very poor solubility and bioavailability. Dr. Chen’s team designed a highly-sensitive fluorescence-based NEP detection system to screen 25 curcumin analogs for their ability to upregulate NEP activity. They found in both mouse and cell models that polyhydroxycurcuminoids, but not curcumin itself, upregulated NEP activity.

They also found that feeding mice polyhydroxycurcuminoids upregulated NEP, decreased Aβ accumulation, and reduced the number of senile plaques in the hippocampus and cortex regions in the brain. Thus, these polyhydroxycurcuminoids represent a promising strategy in the prevention of Alzheimer’s disease.

The full research article entitled “Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer’s disease” is available at the Scientific Reports website at: http://www.ncbi.nlm.nih.gov/pubmed/27407064.

Authors : Po-Ting Chen, Zih-ten Chen, Wen-Chi Hou, Lung-Chih Yu, Rita P.-Y. Chen

Updated : 2016.08.18