Drosophila as an In Vivo Model for Human Neurodegenerative Disease

Abstract

With the increase in the ageing population, neurodegenerative disease is devastating to families and poses a huge burden on society. The brain and spinal cord are extraordinarily complex: they consist of a highly organized network of neuronal and support cells that communicate in a highly specialized manner. One approach to tackling problems of such complexity is to address the scientific questions in simpler, yet analogous, systems. The fruit fly, Drosophila melanogaster, has been proven tremendously valuable as a model organism, enabling many major discoveries in neuroscientific disease research. The plethora of genetic tools available in Drosophila allows for exquisite targeted manipulation of the genome. Due to its relatively short lifespan, complex questions of brain function can be addressed more rapidly than in other model organisms, such as the mouse. Here we discuss features of the fly as a model for human neurodegenerative disease. There are many distinct fly models for a range of neurodegenerative diseases; we focus on select studies from models of polyglutamine disease and amyotrophic lateral sclerosis that illustrate the type and range of insights that can be gleaned. In discussion of these models, we underscore strengths of the fly in providing understanding into mechanisms and pathways, as a foundation for translational and therapeutic research.

Opposite effects of 5-HT/AKH and octopamine on the crop contractions in adult Drosophila melanogaster: Evidence of a double brain-gut serotonergic circuitry

“…Finally, it is now universally accepted that Drosophila is a well-known model organism currently being used in translational neuroscience and behavioral research [37,38]. Given the current interest on the gut-brain axis as a primary subject in the “start”of neurodegenerative disorders, such as Parkinson’s disease [39,40,73] and also the importance of microbiota in the gut-brain axis and serotonergic control [74], our research focused on and provides new information on crop contraction mechanisms (as a part of the gut) and the serotonergic control in this fly.…”

“…Drosophila is a well-known model organism, increasingly used in translational neuroscience and behavioral research [37,38]. Given the current interest on the gut-brain axis as a primary subject in the “start “of neurodegenerative disorders, such as Parkinson’s disease [39,40], it was evident that we needed to determine the possible modulatory effect of serotonin on crop contraction rate because in mammals it is known to modulate hypothalamic receptors, which control the size of carbohydrate-rich meals [41] and other aspects of ingestive behavior [42].…”

Drosophila melanogaster: Deciphering Alzheimer's Disease

“…Many cellular processes involved in neurodegeneration including oxidative stress are exhibited in Drosophila. Drosophila also mimics complex age-dependent behaviours such as memory and locomotor ability (25). To turn Drosophila into an AD model, Drosophila employed the use of the UAS-GAL4 system ( Figure 2).…”

Glial contributions to neuronal health and disease: new insights from Drosophila

“…For decades, Drosophila has served as a tractable genetic model to investigate basic molecular mechanisms that underlie neurodegenerative disease pathogenesis (43). The more recent explosion of work related to Drosophila glial cell biology has now poised to us to tackle the role of glia-neuron interactions in the context of disease.…”