While Parkinson’s disease is one of the most common neurological disorders among the geriatric population, a study by the IIT Bombay and the Tata Institute of Fundamental Research (TIFR) reveals for the first time that persons with a family history of the disease have a strong possibility of having Parkinson’s at an early age, something that may not be detected when still young. “A 2008 Help Age India study of elderly homes in Bangalore showed that while at least 40 per cent of the people surveyed had some degree of Parkinson’s, less than four per cent were aware of the condition. Neurologists estimate the occurrence of Parkinson’s to be 70-90 per 100,000, that is, while seven to nine million people suffer from Parkinson’s in India, doctors warn the number will soar as people are living much longer, with little or no awareness. Hence, the major challenge lies in the fact that the disease itself has no cure and is often noticed by people only when it reaches advanced stages,” said principal investigator, Dr Samir Maji from IIT Bombay’s Department of Biosciences and Bioengineering. [related-post] According to experts, alpha-synuclein protein is present in all human brains. It becomes toxic only due to aggregation or accumulation of these proteins in certain neurons, which synthesise an important neuro-transmitter (dopamine) in the mid-brain of the individual. This toxic accumulation of the protein leads to the death of these neurons and loss of dopamine, resulting in severe disorder of the nervous system or Parkinson’s Disease. “Our work will significantly contribute to the understanding of the structure aggregation relationship of this alpha-synuclein. Therefore, our study is an important step towards gaining deeper insights into the toxic mechanism leading to Parkinson’s and would eventually help in devising therapeutics against the disease,” he said. The paper, published in the Journal of Biological Chemistry, shows that mutations or changes in DNA encoding alpha-Synuclein protein in an individual, owing to family history of Parkinson’s, induces it to accumulate and become toxic. “Individuals suffering from familial form of Parkinson’s have mutation or changes in the alpha-synuclein protein, and develop the disease at an early stage in their lives. We studied the effect of the familial mutations on the structure as well as accumulation behaviour of the protein alpha-synuclein. Our findings reveal that the familial mutations cause subtle changes in the structure of alpha-synuclein protein, making it more prone to accumulate and thus become toxic, leading to Parkinson’s. The study thus explains the possible reason for why a person having a mutated alpha-synuclein will have strong chances to develop Parkinson’s symptoms at an early age,” he said. The study also found that the structure of the protein is not much altered near the mutation site but is significantly changed at locations in the protein far from the site of mutation. The change in DNA also makes the protein structure more rigid and compact, facilitating its accumulation, it shows. The researchers have been working on this study for four years and used genetic engineering and gene cloning techniques to create the familial mutations of human alpha-synuclein. mihika.basu@expressindia.com
