What can the humble fruit fly teach us about Alzheimer’s Disease?
ABSTRACT :
Alzheimer’s disease is a devastating progressive neurodegenerative disease whose incidence increases with age and for which there is currently no disease-modifying treatment. According to WHO predictions, there are likely to be 139 million people living with dementia by 2050, costing over 3 trillion USD per year in healthcare costs. Undoubtedly, as global life-expectancy increases, this disease will cripple our society if effective treatments are not found.
Lack of early and sensitive biomarkers and inadequate targeting of disease mechanisms are two key hurdles for effective treatment. Both are addressed in animal models of disease and amongst such models are transgenics like Drosophila melanogaster, the humble fruit fly. Over the last two decades, we have created several transgenic lines that express a variety of disease associated proteins in the fly brain, and explored the impact on neuronal structure, function as well as overall organismal behaviour. We have identified key cellular pathways that become abnormal causing neuronal dysfunction at early stages of disease before pathological hallmarks form. This leads to neuronal degeneration at later stages of disease coinciding with formation of pathological protein aggregates found in brains of patients with Alzheimer’s disease.
From these studies drug targets have been identified to enable development of more effective disease modifying therapeutics. Additionally, knowledge of the evolution of the disease process in affected neurons has paved the way for the next generation of sensitive biomarkers for early disease diagnosis. These models are also highly suitable for high-through put drug screening as part of the pre-clinical drug discovery pipeline. Our ambition is to collaborate with Indian scientists and employ these models as experimental platforms to screen the many medicinal herbs and other Indian ayurvedic agents that are believed to have therapeutic value, without the attendant side-effects of Western allopathic medicines. In addition to our fly models of Alzheimer’s disease, we also have models of Parkinson’s disease, Huntington’s disease and Traumatic Brain disease, which can all be employed in this way. Using ancient knowledge in modern medicine, this collaboration could thus highli ght key naturopathic therapies and transform the treatment of several neurodegenerative diseases.
ABOUT THE SPEAKER:
Professor of Neurosciences. School of Biological Sciences University of Southampton.