Insulin and the Parkinsonian Brain

According to the American Diabetes Association, about 9.3% of the American population has diabetes, with the number rising every year. It is among the top 10 causes of death in the US. Diabetes has a high impact on our society; it’s not surprising that insulin is a household term. Type-2 diabetes is caused by a diet high in fat and sugar and is the result of the body developing a resistance to insulin signaling. Insulin resistance not only creates the abnormal blood glucose levels associated with diabetes, but also impairs central nervous system signaling. Insulin signaling in the dopaminergic (DA) neurons that degenerate in Parkinson’s disease can be inhibited by chronic inflammation and reactive oxygen species (ROS), both of which are elevated in Parkinson’s disease. Conversely, insulin signaling increases dopamine reuptake from the synapse, prevents mitochondrial dysfunction and related ROS production, reduces tau protein accumulation in Lewy bodies, which are characteristic of Parkinson’s, and helps prevent apoptosis by inhibiting the caspase cascade.

ROS such as superoxide, hydroxyl radicals, and hydrogen peroxide are especially important because they are both a product and a cause of both Parkinson’s disease and insulin resistance. ROS damage the cell by reacting with proteins and causing them to misfold and aggregate, damaging DNA, producing lipid peroxides, and triggering apoptosis. DA neurons are particularly susceptible to ROS damage because they contain a larger than average number of mitochondria, which produce ROS during normal processes, and even more when they are dysfunctional in Parkinson’s disease. Additionally, one of  the dopamine degradation pathways that occur in DA neurons produces ROS.

Using the model I am developing, I hope to create a portrait of the diverse interactions between these two diseases and identify the interactions that would be the most sensitive to treatment.

Comments

  1. emparrish says:

    Great project and great post! I did a paper on proteins for a class in the spring and remembering reading briefly about ROSs. I knew they could be associated with brain cell damage but not they could be elevated by Parkinson’s disease. I’m always interested in Parkinson’s research because my grandmother has been coping with it for a number of years and still going strong! I never thought insulin signaling is affected by Parkinson’s, definitely an interesting component of how people are affected by it. I hope the project is progressing well and look forward to looking at the insight it gives into this terrible, yet intriguing disease.