Naslov
DISC1 i FUS: Koagregacija proteina povezanih s mentalnim i neurodegenerativnim bolestima
(DISC1 and FUS: Co-aggregation of proteins from mental and neurodegenerative illness)

Autori
Jeremić, Martina

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, diplomski rad, preddiplomski

Fakultet
Odjel za biotehnologiju

Mjesto
Rijeka

Datum
14.07

Godina
2021

Stranica
36

Mentor
Bradshaw, Nicholas James

Ključne riječi
agregacija proteina ; shizofrenija ; mentalne bolesti ; neurodegenerativne bolesti
(protein aggregation ; schizophrenia ; mental illness ; neurodegenerative disorders)

Sažetak
Chronic mental illnesses (CMI) such as schizophrenia, bipolar disorder or depression have overlapping genetic backgrounds and symptoms. These illnesses are manifested as disruptions of mental health (cognitive, emotional and behavioural) from various etiological factors. As current diagnostic methods are almost entirely dependent on psychiatric evaluation, and given the complexity of the background, it is hard to develop new approaches to research these illnesses. Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) or Alzheimer’s disease are incurable conditions that result in progressive degeneration of nerve cells. These illnesses are well known to be associated with the occurrence of protein aggregation. Recent studies suggest that this same biological state, in which misfolded proteins aggregate, may be found in mental illnesses as well. The Disrupted in Schizophrenia 1 (DISC1) protein has been identified in the insoluble fraction of the brain tissue of patients suffering from schizophrenia, bipolar disorder and depression, implying that DISC1 aggregated. The Fused in Sarcoma protein (FUS) has been found in in the insoluble fraction of the brain tissue of patients suffering from various neurodegenerative illnesses, including ALS and frontotemporal dementia (FTD). Mutations of FUS have been described as contributing to the progress of illnesses. We investigated the interaction of DISC1 with FUS in protein aggregates. We compared wild-type and mutated FUS protein with DISC1 in cultured mammalian cells. This interaction provides information on the biological link between mental illnesses and neurodegenerative disorders. Microscopic examination of cells overexpressing these two proteins showed the co-aggregation of mutant type FUS with DISC1. Additionally, co- aggregation of fragments of DISC1 with the mutant type (mutation on C-terminal tyrosine) FUS protein was examined to determine which domains of this protein are involved in co-aggregation. One of DISC1 region has been seen aggregating in previous researches. We confirmed the importance of this region for aggregation in a different cell line – human neuroblastoma cell line, because it is of greater biological relevance compared to previously seen results in human embryonic kidney cells. The S>C region is another region of DISC1, which showed no aggregates in cells. Combined with FUS protein, it has been seen that the D>I region does not co-aggregate with FUS protein, while the results of the S>C region suggest potential coaggregation, but for now this remains uncertain. The results obtained here, and further research on these proteins could help explain biological connections between neurodegenerative disorders and mental illnesses, overlap in symptoms of these illnesses and the difficulty of making the diagnose.

Izvorni jezik
Engleski

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

POVEZANOST RADA