Decanoic acid extends lifespan and modulates metabolism in models of PLA2G6-associated neurodegeneration

Area of Science:

• Genetics
• Neuroscience
• Biochemistry

Background:

• PLA2G6-associated neurodegeneration (PLAN) is a rare genetic disorder caused by mutations in the PLA2G6 gene.
• PLAN leads to progressive neurodegeneration, impacting cellular functions.
• Current therapeutic options for PLAN are limited.

Purpose of the Study:

• To investigate the therapeutic potential of decanoic acid (DA), a medium-chain fatty acid, in Drosophila melanogaster models of PLAN.
• To elucidate the molecular mechanisms underlying DA's effects in PLAN.

Main Methods:

• Utilized Drosophila melanogaster as a model organism for PLAN.
• Administered decanoic acid (DA) to flies and assessed lifespan, bang sensitivity, and heat shock resistance.
• Performed transcriptional and metabolomic analyses to identify affected pathways.

Main Results:

• DA treatment significantly extended lifespan and improved stress resistance in PLAN model flies.
• Transcriptional analysis revealed DA's impact on key signaling pathways, including Insulin/IGF, mTOR, and mitochondrial function.
• Metabolomic profiling showed significant alterations in gut tissue, implicating pathways like ABC transporters and purine metabolism.

Conclusions:

• Decanoic acid (DA) demonstrates promising therapeutic potential for PLA2G6-associated neurodegeneration (PLAN).
• DA influences multiple cellular pathways relevant to neurodegeneration, including metabolic and stress response pathways.
• Medium-chain fatty acids warrant further investigation as a novel therapeutic strategy for neurodegenerative diseases.