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Epigenetic Evidence Implies Disturbed Proteostasis and Potentially Protein Aggregation in Suicidality
Julija Šmon1, Maja Juković2, Matea Kršanac2
1Institute of Biochemistry & Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Biomolecules
|May 27, 2026
Summary
Disturbed cellular proteostasis, involving protein aggregation, may underlie suicidality and overlap with neurodegenerative and mental illnesses, suggesting new biomarker avenues.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Suicidality is a significant public health issue requiring better biomarkers.
- Protein aggregation and impaired proteostasis are implicated in neurodegenerative and mental illnesses.
- Recent studies show differential methylation in suicide decedents for genes involved in proteostasis.
Purpose of the Study:
- To review evidence linking disturbed proteostasis to suicidality.
- To explore potential overlaps between suicidality, neurodegeneration, and mental illnesses through proteostasis.
- To investigate the role of epigenetic changes in these conditions.
Main Methods:
- Literature review of studies on proteostasis, suicidality, neurodegeneration, and mental illness.
- Analysis of gene methylation data in individuals who died by suicide.
- Examination of evidence for impaired autophagy and ubiquitin-proteasome system in suicidality.
Main Results:
- Genes related to proteostasis (e.g., MAPT, PRKN, DISC1) show altered methylation in suicide decedents.
- Epigenetic changes in these genes are also observed in other neurological disorders.
- Autophagy and ubiquitin-proteasome system dysfunction are increasingly implicated in suicidality.
Conclusions:
- Disturbed proteostasis is hypothesized as a pathological component of suicidality.
- Protein aggregation in suicidality may overlap with mechanisms in major mental illnesses.
- Understanding proteostasis could lead to novel biomarkers for suicidality and related disorders.
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