Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 Phosphorylation

Mdm20 is an auxiliary subunit of the NatB complex, which includes Nat5, the catalytic subunit for protein N-terminal acetylation. The NatB complex catalyzes N-acetylation during de novo protein synthesis initiation; however, recent evidence from yeast suggests that NatB also affects post-translational modification of tropomyosin, which is involved in intracellular sorting of aggregated proteins. We hypothesized that an acetylation complex such as NatB may contribute to protein clearance and/or proteostasis in mammalian cells. Using a poly glutamine (polyQ) aggregation system, we examined whether the NatB complex or its components affect protein aggregation in rat primary cultured hippocampal neurons and HEK293 cells. The number of polyQ aggregates increased in Mdm20 over-expressing (OE) cells, but not in Nat5-OE cells. Conversely, in Mdm20 knockdown (KD) cells, but not in Nat5-KD cells, polyQ aggregation was significantly reduced. Although Mdm20 directly associates with Nat5, the overall cellular localization of the two proteins was slightly distinct, and Mdm20 apparently co-localized with the polyQ aggregates. Furthermore, in Mdm20-KD cells, a punctate appearance of LC3 was evident, suggesting the induction of autophagy. Consistent with this notion, phosphorylation of Akt, most notably at Ser473, was greatly reduced in Mdm20-KD cells. These results demonstrate that Mdm20, the so-called auxiliary subunit of the translation-coupled protein N-acetylation complex, contributes to protein clearance and/or aggregate formation by affecting the phosphorylation level of Akt indepenently from the function of Nat5

Mental health-related stigma discrimination and prejudices among Greek healthcare professionals

Introduction: Research shows that mental health-related stigma, stereotypes, and prejudices have a negative impact on the patients themselves as well as on their families and social entourage. Healthcare professionals, whose expertise and professional ethos are historically acknowledged by public opinion, are expected to play a major role in combating discrimination against psychiatric patients. In this study, we aimed to assess the attitudes of Greek healthcare professionals toward mental illness and people suffering from it. Materials and methods: It is a non-interventional, analytic study, in which 479 health workers from a tertiary hospital in Thessaloniki, Greece, participated. Every single hospital service –except the personnel of the Psychiatric Clinic– was included in our study: from the cleaning service to the administrative staff and the auxiliary staff such as stretcher carriers, food and nutrition services’ staff, and social workers, the nursing staff, and finally the attending physicians, taking into consideration that the psychiatric patient, from the moment he/she enters the hospital, consecutively gets in contact with every work grade of the healthcare establishment. Participants’ attitudes concerning mental illness have been evaluated using the Opinions about Mental Illness Scale (OMI), the Social Distance Scale (SDS), and the Level of Contact Report (LCR-12). Results: Despite the high level of familiarity [as evaluated with LCR-12; mean score (μ): 8.82 ± 1.73], the employees displayed a rather poor willingness to interact with psychiatric patients (as measured with SDS; μ:11.68 ± 4.28), and endorsed significant prejudice toward individuals with mental disorders (assessed using OMI subscales; Social Discrimination μ: 22.99 ± 12.08, Social Restriction μ: 17.45 ± 9.07, Social Care μ: 21.04 ± 4.12, Social Integration μ: 16.38 ± 4.68, Etiology μ: 9.80 ± 4.95). Age and education stood out as the main determinants of participants’ attitudes, with younger and highly educated participants to have shown a relatively refined profile. Conclusion: These results are not significantly improved compared to those of previous decades in Greek healthcare professionals and call for critical reflection and targeted stigma-reduction efforts. Copyright © 2022 Porfyri, Athanasiadou, Siokas, Giannoglou, Skarpari, Kikis, Myroforidou, Anoixa, Zerakis, Bonti, Konsta, Diakogiannis, Rudolf and Deretzi