Dear Colleagues,

Drosophila melanogaster is an established and widely accepted model organism for developmental studies that possesses unique advantages, such as a short lifespan, a simple but evolutionarily conserved nervous system, and a wide variety of transgenic strains and genetic tools. This powerful and advanced genetic toolbox allows for the rapid and reliable generation of transgenic flies, in which the manipulation (loss-of-function, or over-expression) of the gene(s) of interest is performed with unique and unprecedented precision in specific cells, tissues, and organs. Most importantly, over 75% of disease-associated genes in humans have corresponding orthologs in flies, and, remarkably, all key-molecular pathways are highly conserved, with many organ systems in mammals having equivalent systems in Drosophila.

As Drosophila cells age, they lose their ability to maintain proper protein folding and to eliminate misfolded proteins, thus leading to the accumulation of abnormal protein aggregates, and a loss of protein homeostasis (proteostasis). Two major protein degradation systems, the ubiquitin–proteasome system (UPS) and the autophagy system (ATGS), are activated to avoid proteotoxicity, but during aging they are severely impaired. The Atg genes and the pathways that regulate autophagy are highly conserved between Drosophila and many animal species, including mammals, and critical discoveries about the mechanism of autophagy were identified and characterized for the first time in Drosophila. Altogether, the loss of proteostasis is considered as a hallmark of aging and seems to accelerate the onset of neurodegenerative diseases. Flies exhibit aging behaviors comparable to human aging, and, therefore, many transgenic models of specific neurodegenerative pathologies have been produced to elucidate the role(s) of autophagy in disease initiation, progression, and therapy response(s). Finally, evidence is being accumulated to strongly suggest that the (mid-)gut microbiome also critically contributes to longevity, in all species examined thus far.

Hence, high levels of genomic/genetic conservation combined with a wealth of cellular, genetic, and molecular resources render Drosophila an ideal model for studying neurodegeneration in vivo, and for illuminating the effects of aging in a significantly more reasonable time frame. Taken together, all types of studies related to autophagy, neurodegeneration, and aging in Drosophila are of major interest to this Special Issue.

Dr. Athanassios D. Velentzas
Dr. Dimitrios J. Stravopodis
Dr. Panagiotis D. Velentzas
Guest Editors

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• autophagy
• apoptosis
• brain–gut axis
• brainopathies
• development
• Drosophila model of human diseases
• microbiome
• mitophagy
• necrosis
• neurodegenerative diseases
• proteostasis
• signaling
• ubiquitin–proteasome system