microRNAs in CNS Development and Neurodegeneration: Insights from Drosophila Genetics

Abstract

Age-related neurodegeneration can profoundly impair quality of life in the elderly. Although the causes of many types of familial neurodegenerative diseases are known, genetic forms of disease affect relatively few people. For most people, age is the most prominent risk factor for developing neurodegenerative disease, and very little is known about its molecular causes. Recent advances have linked small regulatory RNA molecules, called microRNAs, to neurodegenerative disorders in animal models, including the fruit fly, Drosophila. Although a fly's brain is vastly simpler than a human brain, much is similar at the level of individual cells and fly models are proving to be useful to understanding the mechanisms that underlie neurodegenerative disease. Our aim is to understand the basic cellular processes that can cause neurodegeneration in the fly model as a means of identifying new links to disease. We are engaged in a large-scale effort to systematically analyze the roles of microRNA genes in the fly brain. The comparative ease and speed with which Drosophila can be studied in the laboratory allow the possibility of a survey of its entire genome for the microRNAs that are required for proper cognitive function and the health and survival of the cells of the brain. Identification of the targets of such microRNAs may help to identify new causes of neurodegenerative disease.