Abstract Presentation

Metabolic Alterations in a Drosophila Model of

Parkinson’s Disease Based on DJ-1 Deficiency
• Solana-Manrique et all., 2022, Journal Cells, Spain
• Parkinson’s disease (PD) is the second-most common neurodegenerative disorder, whose
physiopathology is still unclear. Moreover, there is an urgent need to discover new biomarkers and
therapeutic targets to facilitate its diagnosis and treatment. Previous studies performed in PD
models and samples from PD patients already demonstrated that metabolic alterations are
associated with this disease. In this context, the aim of this study is to provide a better
understanding of metabolic disturbances underlying PD pathogenesis. To achieve this goal, we
used a Drosophila PD model based on inactivation of the DJ-1β gene (ortholog of human DJ-1).
Metabolomic analyses were performed in 1-day-old and 15-day-old DJ-1β mutants and control
flies using 1H nuclear magnetic resonance spectroscopy, combined with expression and enzymatic
activity assays of proteins implicated in altered pathways. Our results showed that the PD model
flies exhibited protein metabolism alterations, a shift fromthe tricarboxylic acid cycle to glycolytic
pathway to obtain ATP, together with an increase in the expression of some urea cycle enzymes.
Thus, these metabolic changes could contribute to PD pathogenesis and might constitute possible
therapeutic targets and/or biomarkers for this disease.
Mitigation of the age-dependent decline in
mitochondrial genome integrity
• Tsai et al., 2022, US, bioRxIV
Unknown processes promote accumulation of mitochondrial DNA mutations during aging. Accumulation of
defective mitochondrial genomes is thought to promote progression of heteroplasmic mitochondrial diseases and
degenerative changes with natural aging. We used a heteroplasmic Drosophila model to test 1) whether purifying
selection acts to limit the abundance of deleterious mutations during development and aging, 2) whether quality
control pathways contribute to purifying selection, 3) whether activation of quality control can mitigate
accumulation of deleterious mutations, and 4) whether improved quality control improves healthspan. We show
that purifying selection operates during development and growth, but is ineffective during aging. Genetic
manipulations suggest that a quality control process known to enforce purifying selection during oogenesis also
suppresses accumulation of a deleterious mutation during growth and development. Flies with nuclear genotypes
that enhanced purifying selection sustained higher genome quality, retained more vigorous climbing activity and
lost fewer dopaminergic neurons. Pharmacological enhancement of quality control produced similar benefits.
Importantly, similar pharmacological treatment of aged mice reversed age-associated accumulation of a
deleterious mtDNA mutation. Our findings reveal dynamic maintenance of mitochondrial genome fitness, and
reduction in the effectiveness of purifying selection during life. Importantly, we describe interventions that
mitigate and even reverse age-associated genome degeneration in flies and in mice. Furthermore, mitigation of
genome degeneration improved wellbeing in a Drosophila model of heteroplasmic mitochondrial disease.
Characterization of sleep‐related neurochemicals in the different
developmental stages and insomnia models of Drosophila
melanogaster
• Sun et all., 2022, China, Biomedical Chromatography
• Neurotransmitters play an important role in regulating the physiological activity of the animal,
especially in emotion and sleep. While nucleotides are involved in almost all cellular processes.
However, the characteristics of sleep-related neurochemicals under different life cycles and
environment remain poorly understood. A rapid and sensitive analytical method was established
with LC-MS/MS to determine eight endogenous neurochemicals in Drosophila melanogaster and
the levels of neurochemicals in the different developmental stages of Drosophila melanogaster
were evaluated. The results indicated that there were significant discrepancies among different
stages, especially from pupal stage to adult. The levels of these compounds in caffeine-induced
insomnia model of Drosophila melanogaster were investigated. Compared with normal group the
eight endogenous metabolites did not fluctuate significantly in insomnia Drosophila melanogaster,
which may be due to the mechanism of caffeine-induced insomnia through other pathways, such
as adenosine. The results provide a reference for decoding of neurochemicals involved in the
development of the full cycle of mammalian life and exploration of insomnia even other mental
diseases induced by exogenous substances in the future.