A scientist from Jubilee Mission Medical College, Thrissur, has made a breakthrough in Alzheimer’s disease (AD) drug research, one of the most common, progressive neurodegenerative disorders affecting the elderly.
Dileep Vijayan, Laboratory for Computational and Structural Biology, Jubilee Centre for Medical Research, Thrissur, has made progress in research in association with scientists from RIKEN, a Japanese research institution.
Though pathologies of AD have been well studied, the treatment has been highly challenging due to the scarcity of the number of drugs. Tacrine, the first marketed drug for AD, reversibly inhibits the enzyme acetylcholinesterase (AChE). AChE is an enzyme involved in the rapid breakdown of the neurotransmitter acetylcholine, thus promoting AD.
However, due to hepatotoxicity (damage to liver), Tacrine has been withdrawn from market. Still, Tacrine is being used as a potential starting point to design highly efficient anti-AD drug without hepatotoxicity, according to Dr. Vijayan.
Molecules that inhibit AChE have pharmacological importance as they can be used for the treatment of cholinergic deficits (disturbance in attention and cognition) in neurodegenerative disorders such as AD.
“Since there are high structural similarities between the acetylcholinesterase from humans and that of pacific electric ray fish (electric eel), the majority of researches has been performed with electric eel acetylcholinesterase, considering it a surrogate model. In 1993, Israeli scientists demonstrated how Tacrine binds to acetylcholinesterase isolated from the electric eel. However, the binding of Tacrine with human acetylcholinesterase was unknown for almost three decades.”
The current research by Dr. Vijayan and his team has unlocked this mystery. The collaborative research has unveiled the atomic level binding mode of Tacrine with human acetylcholinesterase. Their research findings have been published in the Elsevier-owned journal International Journal of Biological Macromolecules.
Dr. Vijayan and his group is now anticipating that their research might provide new dimensions to Alzheimer’s drug discovery. With financial support of Central government agencies such as the Department of Biotechnology and Spices Board, Dr. Vijayan and his team is now trying to develop potential drug molecules for AD.
AD is exacting a high socio-economic burden on society due to the increased number of patients. Based on available facts and figures, the Alzheimer's Disease International Federation has predicted the number of AD patients to be 131.5 million by 2050.
