Naslov
DISC1 and TRIOBP-1: co-aggregation partners in schizophrenia

Autori
Juković, Maja ; Zaharija, Beti ; Samardžija, Bobana ; Bradshaw, Nicholas J.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts, 29th International Student Congress Of (bio)Medical Sciences / - , 2022, 436-436

Skup
29th International Student Congress Of (bio)Medical Sciences

Mjesto i datum
Groningen, Nizozemska, 08.06.2022. - 10.06.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
DISC1 ; TRIOBP-1 ; mental illness ; schizophrenia ; protein aggregation

Sažetak
Introduction Schizophrenia is one of the major chronic mental illnesses, and it presents with persistent disturbances in cognitive processes, social interaction, and emotional responsiveness. The treatments currently available are insufficient and mostly focused on diminishing the symptoms, rather than treating the cause. Recently, stemming from the research of neurodegenerative disorders, we and others proposed disrupted proteostasis and aggregate formation as a possible mechanism for non-genetic causes of schizophrenia onset. The proteins we studied, Disrupted in Schizophrenia 1 (DISC1), and TRIO-Binding Protein, splice variant 1 (TRIOBP-1), were previously seen to aggregate in a subgroup of schizophrenia patients. However, while they aggregate separately in patients, it is unclear if they co-aggregate together. Materials & Methods DISC1, wild type TRIOBP-1 and its non-aggregating mutant were fused with EGFP or FLAG-tag, and verified by Western blot. DISC1 was overexpressed in neuroblastoma cell line, SH-SY5Y, on its own and with either wild type or mutant TRIOBP-1. Presence of (co)-aggregates was determined using fluorescent microscopy and CellSens software. All of the results were repeatable (n=3), independent of tags/fusion proteins used and verified by using negative controls. Results Both DISC1 and TRIOBP-1 were confirmed to aggregate when overexpressed in the neuroblastoma cells on their own. Additionally, upon their co- expression, their aggregates were seen to colocalize in the cells, therefore implying these proteins co-aggregate. Experiments with wild type DISC1 and a non-aggregating TRIOBP-1 mutant (60- 652, Δ333-340) suggest that mutant TRIOBP-1 stabilizes DISC1, hindering its aggregation, and in turn DISC1 induces TRIOBP-1 aggregation. These results propose that DISC1 and TRIOBP-1 might be interaction partners as well as co-aggregation partners. Conclusion One of the main issues surrounding early and reliable diagnosis of schizophrenia is the lack of biomarkers. These newly-discovered co-aggregates could potentially lead to advances in the research of disrupted proteostasis as a possible underlying biological cause of non-genetic schizophrenia causes. Further experiments are required to propose a possible mechanism by which the co- aggregation occurs, and eventually how to prevent it. Lastly, protein co-aggregates could possibly be detected in the bloodstream or cerebrospinal fluid of schizophrenia patients, and serve as diagnostic biomarker or even make a conceivable drug target for more effective schizophrenia treatment.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA