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Selective Autophagy as a Potential Therapeutic Target in Age-Associated Pathologies
Margarita-Elena Papandreou1,2, Nektarios Tavernarakis1,2
1Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, 70013 Heraklion, Greece.
Abstract:
Progressive accumulation of damaged cellular constituents contributes to age-related diseases. Autophagy is the main catabolic process, which recycles cellular material in a multitude of tissues and organs. Autophagy is activated upon nutrient deprivation, and oncogenic, heat or oxidative stress-induced stimuli to selectively degrade cell constituents and compartments. Specificity and accuracy of the autophagic process is maintained via the precision of interaction of autophagy receptors or adaptors and substrates by the intricate, stepwise orchestration of specialized integrating stimuli. Polymorphisms in genes regulating selective autophagy have been linked to aging and age-associated disorders. The involvement of autophagy perturbations in aging and disease indicates that pharmacological agents balancing autophagic flux may be beneficial, in these contexts. Here, we introduce the modes and mechanisms of selective autophagy, and survey recent experimental evidence of dysfunctional autophagy triggering severe pathology. We further highlight identified pharmacological targets that hold potential for developing therapeutic interventions to alleviate cellular autophagic cargo burden and associated pathologies.
Insights
Cellular damage accumulation drives aging diseases. Selective autophagy dysfunction contributes to pathology, but targeting it may offer therapeutic benefits for age-related conditions.
Area of Science:
- Cellular Biology
- Molecular Biology
- Gerontology
Background:
- Progressive accumulation of damaged cellular components is a hallmark of aging and contributes to age-related diseases.
- Autophagy, a fundamental catabolic process, is crucial for recycling cellular material across various tissues and organs.
- Dysfunctional autophagy, particularly selective autophagy, is increasingly linked to severe pathologies and aging processes.
Purpose of the Study:
- To elucidate the modes and mechanisms of selective autophagy.
- To review experimental evidence linking autophagy perturbations to severe pathologies.
- To identify potential pharmacological targets for therapeutic interventions in autophagy-related disorders.
Main Methods:
- Literature review of selective autophagy mechanisms.
- Survey of experimental data on dysfunctional autophagy.
- Analysis of identified pharmacological targets for therapeutic potential.
Main Results:
- Selective autophagy ensures cellular homeostasis by precisely degrading damaged constituents.
- Polymorphisms in genes regulating selective autophagy are associated with aging and age-related disorders.
- Evidence highlights severe pathologies arising from impaired autophagy.
Conclusions:
- Pharmacological modulation of autophagic flux presents a promising therapeutic strategy for age-related diseases.
- Targeting specific pathways in selective autophagy may alleviate cellular cargo burden and associated pathologies.
- Understanding and manipulating selective autophagy is key to combating age-related cellular dysfunction.
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