Drosophila as a model to study autophagy in neurodegenerative diseases and digestive tract

Abstract

Autophagy regulates cellular homeostasis by degrading and recycling cytosolic components and damaged organelles. Disruption of autophagic flux has been shown to induce or facilitate neurodegeneration and accumulation of autophagic vesicles is overt in neurodegenerative diseases. The fruit fly Drosophila has been used as a model system to identify new factors that regulate physiology and disease. Here we provide a historical perspective of how the fly models have offered mechanistic evidence to understand the role of autophagy in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Charcot-Marie-Tooth neuropathy, and polyglutamine disorders. Autophagy also plays a pivotal role in maintaining tissue homeostasis and protecting organism health. The gastrointestinal tract regulates organism health by modulating food intake, energy balance, and immunity. Growing evidence is strengthening the link between autophagy and digestive tract health in recent years. Here, we also discuss how the fly models have advanced the understanding of digestive physiology regulated by autophagy.

Lysosome-acidifying nanoparticles rescue A30P α-synuclein induced neuronal death in cellular andDrosophilamodels of Parkinson’s disease

“…Optimization of available lead compounds and nanomedicine as well as launching of new drug screen studies such as using artificial lysosomes loaded with trypsin (51, 52) may provide more effective lysosome-targeting therapeutics that can potentially be applied to PD. Furthermore, future studies may include direct in vivo monitoring of autolysosomal acidification dysfunction in PD using autolysosomal reporter flies (53) and mice (54).…”

CIERMMI Women in Science T-XVIII Health Sciences

“…Additionally, about 75% of the genes involved in human diseases have their homologue in D. melanogaster (Yamamoto et al, 2014), making it an excellent prospect for studying neuronal dysfunction and neuronal death derived from various neurodegenerative diseases (Chan & Bonini, 2000). Some neurodegenerative disorders studied in Drosophila include Alzheimer, Parkinson, tauopathies, ALS, prions (PrD), dystonia, noncoding expansions (SCA8, myotonic dystrophy), some recessive disorders including fragile X syndrome and Friedreich's ataxia, and various polyglutamine disorders (Huntington disease, SCA1, SCA3, and spinobulbar muscular atrophy) (Xu et al, 2015;Tzou et al, 2022).…”

Modelling of human polyglutamine neurological disorders in Drosophila

“…Additionally, about 75% of the genes involved in human diseases have their homologue in D. melanogaster (Yamamoto et al, 2014), making it an excellent prospect for studying neuronal dysfunction and neuronal death derived from various neurodegenerative diseases (Chan & Bonini, 2000). Some neurodegenerative disorders studied in Drosophila include Alzheimer, Parkinson, tauopathies, ALS, prions (PrD), dystonia, noncoding expansions (SCA8, myotonic dystrophy), some recessive disorders including fragile X syndrome and Friedreich's ataxia, and various polyglutamine disorders (Huntington disease, SCA1, SCA3, and spinobulbar muscular atrophy) (Xu et al, 2015;Tzou et al, 2022).…”