In a breakthrough, researchers from the University of Delhi found that the progression of Alzheimer’s and Parkinson’s diseases can be suppressed or stopped by downregulating the expression level of d-myc in Drosophila (fruit fly). Since d-myc in an evolutionarily conserved human homolog of c-myc proto-oncogene, the findings in fruit fly may be applicable to humans as well. Results of a study were published on March 21 in the journal Molecular Neurobiology.
Alzheimer’s and Parkinson’s diseases occur due to accumulation of abnormal clumps of proteins in neuronal cells. The abnormal clumps are formed when a mutation to tau protein acts as a trigger and causes the addition of more phosphate group to the tau protein. The addition of more phosphate group (phosphorylation) to the tau protein causes it to fold into the wrong shape and stick together to form fibre-like structure, which eventually bundle up to form clumps (neurofibrillary tangles) of proteins in the affected brain cells.
“Our team focussed on finding an appropriate gene/protein which can be utilized as an effective drug target to suppress or stop the pathogenesis and manifestation of Alzheimer’s and Parkinson’s diseases by reducing or preventing protein clumps from being formed in the brain cells,” said Dr. Surajit Sarkar from the Department of Genetics, University of Delhi. “We screened over 1000 genes in Drosophila and found d-myc as a candidate gene that was restricting the pathogenesis of Alzheimer’s and Parkinson’s diseases.”
Most of the attempts at drug development have failed in the past, in part, because of the difficulties in finding an appropriate target gene or protein to act upon. Not anymore. Dr. Sarkar’s team has successfully zeroed in on d-myc in fruit flies (c-myc proto-oncogene in humans) as a possible target gene.
The c-myc proto-oncogene in humans is a global regulator of gene expression. When this gene is down regulated, it prevents other genes from enabling more phosphate group to get added to the tau protein, thereby restricting/stopping the progression of disease.
Since a majority of anti-cancer drugs attempts to regulate c-myc proto-oncogene expression, the use of such drugs in people with early stages of Alzheimer’s and Parkinson’s disease can help in stopping the progression of the disease.
“Our study demonstrates for the first time that a common drug target (c-myc proto-oncogene) can be used to treat two most devastating human disorders — cancer, and Alzheimer’s and Parkinson’s diseases,” Dr. Sarkar said.
Interestingly, several reports of successful clinical trials using certain anti-cancer drugs to treat Alzheimer’s and Parkinson’s appeared just as his team concluded the experimental work. “These scientists used anti-cancer drugs without knowing how and why the drugs were effective. Now, our study shows why the drugs helped in treating Alzheimer’s and Parkinson’s diseases,” he said.
Cellular and molecular investigations were carried out in fruit fly as undertaking such studies on human subjects is unethical. Also, brain tissues are completely degenerated in people with Alzheimer’s who have died.
The fruit fly was genetically programmed to develop symptoms of Alzheimer’s and Parkinson’s disease. Interestingly, expression of human’s Alzheimer’s or Parkinson’s disease causing gene in fruit flies shows symptoms similar to human Alzheimer’s or Parkinson’s — death of brain cells, memory loss, disability in movement, early death.