20.500.12556/RUL-182898 Epigenetic evidence implies disturbed proteostasis and potentially protein aggregation in suicidality Suicide is a major public health concern and cause of death worldwide. While progress has been made in understanding molecular pathways involved in suicide, much more work is needed to identify clinically useful biomarkers of suicidality. Disturbed cellular proteostasis and aggregation of specific misfolded proteins are established pathological factors of neurodegenerative diseases. Increasing evidence also suggests that such aggregates often occur in patients with chronic mental illnesses. Recently, genes related to disturbed proteostasis showed differential methylation in individuals who died by suicide compared to controls. These include five genes encoding proteins that aggregate in neurodegenerative and/or mental illness: CRMP1 (also called DPYSL1), DISC1, MAPT (encoding the Tau protein), PRKN (also called PARK2, encoding Parkin), and SOD1. Given the possibility that altered methylation in these genes could affect expression of the proteins they encode, we aimed to review evidence for whether disturbed proteostasis may be a point of overlap between suicidality, neurodegenerative disease, and/or mental illnesses. Epigenetic changes in most of these genes also occur in other neurological disorders. Autophagy, and, to a lesser extent, the ubiquitin-proteasome system, are emerging as potentially impaired in individuals with suicidal tendencies and individuals who died by suicide. Based on this accumulated data, we hypothesise that disturbed proteostasis is likely to be a pathological component of suicidality. It is also plausible that this may lead to the accumulation of aggregated proteins in a similar manner to, and potentially overlapping with, those seen in major mental illnesses. If true, this would have consequences for potential identification of biomarkers for suicidality and should be a priority for future research in the field. epigenetics protein aggregation proteostasis suicide epigentika agregacija proteinov proteostaza samomor true false true Angleški jezik Slovenski jezik Članek v reviji 2026-05-27 19:53:38 2026-05-27 19:53:48 2026-07-07 04:17:35 0000-00-00 00:00:00 2026 0 0 30 str. iss. 5, art. 733 Vol. 16 May 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.2 2218-273X 10.3390/biom16050733 279590915 RAZ_Smon_Julija_2026.pdf RAZ_Smon_Julija_2026.pdf 1 2672CB31C12801827415BE504FA3491F 284c99e2453979f91c786ff3517cb896e2b07c62333cdf3d8da51ff78556af53 7cfd2a37-794f-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=237200 https://www.mdpi.com/2218-273X/16/5/733 1 acde8fd3-59f4-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=234548 Medicinska fakulteta 0 0 0