The effects of neurodegenerative diseases can be devastating for patients and their families. In 2007, the United Nations stated that 1 in 6 people in the world are affected by neurological disorders including diseases like Huntington’s, Alzheimer’s, and amyotrophic lateral sclerosis (ALS). With over 600 characterized neurological disorders yet very few treatments, it is imperative that continued research efforts elucidate the mechanisms underlying these diseases in the hopes of developing targeted and effective treatments. As part of the FlyBook inaugural chapters published in the October issue of GENETICS, McGurk et al. put forth the fly as an in vivo model for human neurodegenerative disease and describe how the fly is a vital tool for providing mechanistic insight.

As most Biology 101 students can tell you, the fly has been a widely-used tool in biological research for over 100 years! Gene manipulation in Drosophila can be fast and relatively simple, and, with short generation times, fly lines are maintained with relative ease. Additionally, fly models offer unique advantages specific to studies of the nervous system, as the organism has a central nervous system that bears striking similarities to that of mammals, though is less complex.  The Drosophila genome is also much smaller than the human genome, allowing easier interpretation of results from gene manipulation studies.

McGurk et al. adds to previous reviews on the subject of fly models of neurodegenerative disease by focusing and describing select studies to emphasize the strengths of such approaches. To do this, McGurk et al. describe studies on polyQ diseases and ALS. PolyQ diseases, a group of diseases that include Huntington’s, are characterized by the expansion of a CAG trinucleotide repeat within the respective gene. Transgenic flies that express the expanded repeat mutation show neurodegenerative effects remarkably reminiscent to those seen in humans. These studies illustrate the power of fly to recapitulate human disease features, providing a system with which to elucidate causal genetic mechanisms.

ALS, also known as Lou Gehrig’s Disease, is the most prevalent of a group of motor neuron diseases that involve the death of neurons. Affecting as many as 30,000 Americans, ALS onsets in individuals as adults, impacting the spinal cord and leading to paralysis and, ultimately, death. For the most part, the cause of this tragic disease has been veiled in mystery for decades, but recent advances in identifying the genetic underpinnings of the disease have been facilitated by enhanced genomic technologies. These findings indicate that many genes related to the disease are involved in RNA biology, suggesting that such activities are involved in the pathology of the disease. Focusing on one such identified gene, TDP-43, McGurk et al. illustrate the power of fly models to investigate this disease. Fly studies for example, were critical for the identification of ATAXIN-2 as a gene that modifies, and consequently adjusts the toxicity of, TDP-43. Researchers proceeded to investigate this modifier and found that mutations in this gene were regularly found in ALS patient populations, characterizing it as a definitive ALS disease gene. This illustrates the impact of combining findings from model organisms with those of genetic analyses to expand our understanding of disease.

Although flies look quite different from humans, flies share a remarkable amount of similarity to mammalian neurodegenerative disease pathologies. The examples described by McGurk et al. illustrate the power of such models and the breadth of understanding that can come from them.  With the necessity for the development of therapeutics for the hundreds of neurological disorders looming, perhaps the solution is in approaches that combine the historic model system of the fruit fly with the sequencing innovations that develop further everyday.

 

CITATIONS:

McGurk, L., Berson A., & Bonini, N. 2015. Drosophila as an In Vivo Model for Human Neurodegenerative Disease. GENETICS, 201 (2): 377-402. doi:http://doi.org/10.1534/genetics.115.179457

Bilen, J., & Bonini, N. 2005. Drosophila as a Model for Human Neurodegenerative Disease. Annual Review of Genetics, 39:153-171. doi:http://doi.org/10.1146/annurev.genet.39.110304.095804

, , ,

GSA science writing intern. Grad student in Evolution, Ecology, and Organismal Biology at UNC Chapel Hill.

View all posts by Kayleigh O'Keeffe »

Read more in

  • Ed Grell at his dissecting microscope using ether to anesthetize his flies.

    In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation

    Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…

  • Congratulations to the #Fungal24 Poster Award winners!

    We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…

  • Poster presentation tips for TAGC 2024

    You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…

  • Maximize your TAGC 2024 experience 

    A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…

  • Early Career Leadership Spotlight: Sarah Petrosky

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…

  • TAGC 2024 Early Career Award Winners

    GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024.  Don’t miss the opportunity…

  • Preeminent geneticists recognized with revamped GSA Awards

    In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…

  • Fly Board funds outreach programs to spread the word about Drosophila research

    In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…

  • New members of the GSA Board of Directors: 2024–2026

    We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…

  • A rose-ringed parakeet, one of three parrot species used in the study.

    Parrot plumage study aids breeders and endangered natural populations

    Yellow coloration is maladaptive in the wild but prized by breeders. People have long been fascinated with birds, which exhibit one of the widest ranges of coloration among vertebrates. Parrots, in particular, have captivated humans by their ability to mimic human speech and spectacular plumage. Brightly colored feathers are used primarily to attract mates, intimidate…

  • Early Career Leadership Spotlight: Sarah Gilmour

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah GilmourMultimedia SubcommitteeStowers Institute for Medical Research Research Interest Questions of evolution have always fascinated me. I am extremely fortunate to be starting out my research career in a…