Sarasota, Fla. Dr. Daniel Paris, a senior scientist of the Roskamp Institute, was awarded an Investigator Initiated Research Grant Award from the Alzheimer’s Association to investigate the preclinical efficacy of a natural compound (celastrol) in a genetically engineered mouse model of Alzheimer’s disease.
The brain of Alzheimer’s disease patients is characterized by the accumulation of a small protein called beta-amyloid or Abeta and by the presence of intraneuronal tangle of a protein called tau. Abeta appears to be a key player in the pathology of Alzheimer’s disease and has been shown to trigger memory impairment, neuronal loss, abnormal tau protein accumulation, as well as cerebrovascular damages in various animal models of the disease. Abeta is produced by the cleavage of a larger protein precursor by two different enzymes called beta and gamma-secretase. Beta-secretase is the rate limiting enzyme in the production of Abeta and is viewed as a golden target for the treatment of Alzheimer’s disease. However despite intensive work, direct inhibitors of beta-secretase or Gamma-secretase with good drug-like properties have been extremely difficult to make. Given the difficulties being encountered by pharmaceutical industries for developing direct secretase inhibitors, Dr. Paris hypothesized that drugs which indirectly target the beta-secretase by affecting the production of the enzyme rather than by inhibiting it would be beneficial. Following the development of a screening method for identifying such drugs, Dr. Paris’ research team identified that a small molecule called celastrol is an indirect beta-secretase inhibitor that can potently oppose the production of Abeta. Celastrol is a natural compound extracted from a perennial creeping plant indigenous to a large area in southern China and known as the “Thunder of god vine”. Extracts containing celastrol have been given to Chinese patients for many years and are known to be efficient against inflammatory conditions. In the present research, Dr. Paris will determine whether celastrol holds promise as a therapeutic agent for the treatment of Alzheimer’s disease. He will further investigate whether this compound can prevent or reverse cognitive deficits, Abeta accumulation and tau pathology that affect a transgenic mouse model of Alzheimer’s disease.
Roskamp is a not-for-profit research Institute located in Sarasota, Fla., that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinic also offers comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.
For more information, please contact the Institute at (941) 752-2949, Roskamp’s Clinical Trials Division in Sarasota at (941) 256-8018 or visit www.mullanalzheimer.com.