Pregled bibliografske jedinice broj: 1152643
Protein Aggregation of NPAS3, Implicated in Mental Illness, Is Not Limited to the V304I Mutation
Protein Aggregation of NPAS3, Implicated in Mental Illness, Is Not Limited to the V304I Mutation // Journal of personalized medicine, 11 (2021), 1070, 18 doi:10.3390/jpm11111070 (međunarodna recenzija, članak, znanstveni)
CROSBI ID: 1152643 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Protein Aggregation of NPAS3, Implicated in Mental
Illness, Is Not Limited to the V304I Mutation
Autori
Samardžija, Bobana ; Pavešić Radonja, Aristea ; Zaharija, Beti ; Bergman, Mihaela ; Rennar, Éva ; Palkovtis, Miklós ; Rubeša, Gordana ; Bradshaw, Nicholas J.
Izvornik
Journal of personalized medicine (2075-4426) 11
(2021);
1070, 18
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni
Ključne riječi
blood serum ; major depressive disorder ; insular cortex ; mental illness ; neuronal PAS protein 3 (NPAS3) ; post‐mortem brain tissue ; protein aggregation ; proteinopathy ; schizophrenia
Sažetak
An emerging phenomenon in our understanding of the pathophysiology of mental illness is the idea that specific proteins may form insoluble aggregates in the brains of patients, in partial analogy to similar proteinopathies in neurodegenerative diseases. Several proteins have now been detected as forming such aggregates in the brains of patients, including DISC1, dysbindin‐1 and TRIOBP‐ 1. Recently, neuronal PAS domain protein 3 (NPAS3), a known genetic risk factor for schizophrenia, was implicated through a V304I point mutation in a family with major mental illness. Investigation of the mutation revealed that it may lead to aggregation of NPAS3. Here we investigated NPAS3 aggregation in insular cortex samples from 40 individuals, by purifying the insoluble fraction of these samples and testing them by Western blotting. Strikingly, full‐length NPAS3 was found in the insoluble fraction of 70% of these samples, implying that aggregation is far more widely spread than can be accounted for by this rare mutation. We investigated the possible mechanism of aggregation further in neuroblastoma cells, finding that oxidative stress plays a larger role than the V304I mutation. Finally, we tested to see if NPAS3 aggregation could also be seen in blood serum, as a more accessible tissue than the human brain for future diagnosis. While no indication of NPAS3 aggregation was seen in the serum, soluble NPAS3 was detected, and was more prevalent in patients with schizophrenia than in those with major depressive disorder or controls. Aggregation of NPAS3 therefore appears to be a widespread and multifactorial phenomenon. Further research is now needed to determine whether it is specifically enhanced in schizophrenia or other mental illnesses.
Izvorni jezik
Engleski
Znanstvena područja
Biologija, Kliničke medicinske znanosti, Biotehnologija, Interdisciplinarne biotehničke znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)
POVEZANOST RADA
Projekti:
--IP-2018-01-9424 - Istraživanje shizofrenije kroz ekspresiju netopivih proteina (CandidIskren) (Bradshaw, Nicholas James) ( CroRIS)
--DOK-2018-09-5395 - Istraživanje shizofrenije kroz ekspresiju netopivih proteina (CandidIskren) (Bradshaw, Nicholas James) ( CroRIS)
--DOK-2020-01-8580 - Istraživanje shizofrenije kroz ekspresiju netopivih proteina (CandidIskren) (Bradshaw, Nicholas James) ( CroRIS)
Ostalo-V-8151/17016 - Equipment subsidy / Gerätebehilfen (Bradshaw, Nicholas James, Ostalo ) ( CroRIS)
Ustanove:
Medicinski fakultet, Rijeka,
Klinički bolnički centar Rijeka,
Sveučilište u Rijeci - Odjel za biotehnologiju
Profili:
Beti Zaharija
(autor)
Bobana Samardžija
(autor)
Nicholas James Bradshaw
(autor)
Gordana Rubeša
(autor)