Phosphorylation of Neuronal Proteins in Drosophila melanogaster Changes With Age

Abstract

Cells, such as epithetical and red blood cells, have the capacity to regenerate throughout an organism's lifetime. However, neurons are unique because they do not regenerate; once most neurons are formed, they last the lifetime of an organism. This lack of regeneration is the reason that neurodegenerative diseases, including Alzheimer's Disease and Huntington's Disease, are so detrimental; the diseases target cells that can't be replaced if they're damaged. These diseases occur later in life, which indicates a problem with the normal aging process of neurons; these diseases are associated with abnormal protein accumulation. There are housekeeping genes that are associated with normal cell upkeep; this upkeep can happen by protein degradation by either proteosomal digestion or autophagy. The two degradation pathways are quality control mechanisms that allow for degradation of abnormal or old proteins without destroying the undamaged proteins, which allows for longevity in structures such as neurons. As neurons age, they acquire intracellular aggregates despite these degradation pathways, and some of these aggregates are key features of neurodegenerative diseases. We are interested in understanding how well degradation pathways work in neurons of different ages, and what changes in older cells lead to intracellular aggregates. One key way to understand how neurons age is to investigate how neuronal proteins change over time. Changes in protein abundance or post‐translational modification of existing proteins could severely affect how cells deal with the stresses of aging. To determine how proteins change with age, protein levels and post‐translational modifications are compared between young and old neurons to determine how the same protein could differ over time. The changes are then analyzed in order to identify post‐translational modifications that are important for healthy neuronal aging and investigate the functional significance of the modifications. We have focused on identifying changes in protein phosphorylation between young and old brains in wild type Drosophila melanogaster by two dimensional gel electrophoresis and liquid chromatography mass spectroscopy. Preliminary results have found increased levels of protein phosphorylation in old Drosophila melanogaster heads. Once we analyze these findings through mass spectroscopy, we will be able to identify the exact proteins that differ in order to study their function in Drosophila.