The Tiny Drosophila Melanogaster for the Biggest Answers in Huntington’s Disease

Abstract

The average life expectancy for humans has increased over the last years. However, the quality of the later stages of life is low and is considered a public health issue of global importance. Late adulthood and the transition into the later stage of life occasionally leads to neurodegenerative diseases that selectively affect different types of neurons and brain regions, producing motor dysfunctions, cognitive impairment, and psychiatric disorders that are progressive, irreversible, without remission periods, and incurable. Huntington’s disease (HD) is a common neurodegenerative disorder. In the 25 years since the mutation of the huntingtin (HTT) gene was identified as the molecule responsible for this neural disorder, a variety of animal models, including the fruit fly, have been used to study the disease. Here, we review recent research that used Drosophila as an experimental tool for improving knowledge about the molecular and cellular mechanisms underpinning HD.

Latrophilins: A Neuro-Centric View of an Evolutionary Conserved Adhesion G Protein-Coupled Receptor Subfamily

“…Neuronal axons have all the machinery necessary to transmit nerve impulses in a similar way to how action potentials are generated in mammals leading to neurotransmitter release at the synapses (Jekely et al, 2018; Kasture et al, 2018; Rich and Terman, 2018; Sugie et al, 2018). Hence, Drosophila offers a good model to study neuronal proteins (Monnier et al, 2018; Rosas-Arellano et al, 2018). Drosophila melanogaster only has a single homolog of latrophilins (Scholz et al, 2015).…”

Adenosine receptor and its downstream targets, mod(mdg4) and Hsp70, work as a signaling pathway modulating cytotoxic damage inDrosophila

“…To characterize the involvement of Ado signaling in the stress response, we used mHTTexpressing flies as a well-characterized genetic model for neurodegeneration and cytotoxic stress (Rosas-Arellano et al, 2018). We initially examined flies overexpressing normal exon 1 from human huntingtin (Q20 HTT), or its mutant pathogenic form (Q93 mHTT), driven by the ubiquitous daughterless-Gal4 (da-Gal4) and pan-neuron driver (elav-Gal4).…”

Metabolomic Nuclear Magnetic Resonance Studies at Presymptomatic and Symptomatic Stages of Huntington’s Disease on a Drosophila Model

“…17 HD animal models have been developed in various organisms such as mouse, [18][19][20] rat, 17,21,22 sheep 23 or invertebrates such as the fruit fly Drosophila. [24][25][26] Here we selected Drosophila as this model organism is well-established to study human diseases. Drosophila are easy to handle and many approved genetic tools are available for transgenesis and gene expression / inactivation in specific cell and tissue types.…”

“…Although its brain appears to be simple compared to mammals, Drosophila display complex behaviors such as learning and memory, sleep or courtship. 25 In addition, its nervous system is composed of various types of neurons (dopaminergic, serotonergic, glutamatergic, GABAergic …) and glia as in vertebrates. Numerous models of neurodegenerative diseases, including Parkinson's or Alzheimer's diseases, have been developed in Drosophila.…”