Naslov
Proteini interakcijski partneri TRIOBP-1 i njegov učinak na njihovu agregaciju u shizofreniji
(Protein interaction partners of TRIOBP-1, and its effect on their aggregation in schizophrenia)

Autori
Juković, Maja

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, diplomski rad

Fakultet
Odjel za biotehnologiju

Mjesto
Rijeka

Datum
08.09

Godina
2021

Stranica
75

Mentor
Bradshaw, Nicholas James

Ključne riječi
Kronične mentalne bolesti ; agregacija proteina ; TRIO-Binding Protein splice variant 1 (TRIOBP-1) ; Disrupted in Schizophrenia 1 (DISC1) ; Nuclear Distribution Element 1 (NDE1)
(Chronic mental illness ; protein aggregation ; TRIO-Binding Protein splice variant 1 (TRIOBP-1) ; Disrupted in Schizophrenia 1 (DISC1) ; Nuclear Distribution Element 1 (NDE1))

Sažetak
Chronic mental illnesses are a group of conditions that include major depressive disorder, bipolar disorder and schizophrenia. These illnesses present with persistent psychiatric symptoms and affect 10.7% of the global population. The emphasis of this thesis is on schizophrenia and disrupted proteostasis as its possible source. This idea stemmed from recent studies that proposed that insoluble, misfolded proteins deposits may not be limited to neurodegenerative disorders, but exist in chronic mental illnesses as well. Several proteins are being investigated for their propensity to aggregate, however, it remains unclear whether these proteins aggregate alone, co-aggregate with each other or recruit other proteins as a part of the pathological processes. In this thesis we studied the propensity of TRIOBP-1 to aggregate alone and its ability to recruit other proteins to co-aggregate by overexpressing these proteins in neuroblastoma cells. In the first part of research we tested TRIOBP-1 with six of its potential interaction partners, out of which only NDE1 was seen to co- aggregate. Hence, we propose the aggregation mechanism implicating TRIOBP-1 misassembly as responsible for recruiting NDE1 to co-aggregate as well. The second portion of the study focused on researching TRIOBP-1 co-aggregation partners among the proteins previously implicated in chronic mental illness. In these experiments, only DISC1 co-aggregated with TRIOBP-1. Experiments with non- aggregating TRIOBP-1 mutant suggest these proteins are interaction partners as well as co-aggregation partners. Two out of ten tested proteins were seen to co- aggregate with TRIOBP-1, however, other proteins are not yet to be excluded from their possible involvement in schizophrenia. These newly discovered insoluble deposits could act as a potential biological markers and used for early schizophrenia diagnosis V if discovered not to be limited to the brain. They may also provide a valuable insight in underlaying mechanism of non-genetic schizophrenia onset.

Izvorni jezik
Engleski

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

POVEZANOST RADA