Next Article in Journal
Mapping Compound Databases to Disease Maps—A MINERVA Plugin for CandActBase
Previous Article in Journal
Psychological Stress and Salivary Cortisol Levels in Patients with Plaque Psoriasis
Article

Protein Aggregation of NPAS3, Implicated in Mental Illness, Is Not Limited to the V304I Mutation

1
Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia
2
Psychiatry Clinic, Clinical Hospital Centre Rijeka, 51000 Rijeka, Croatia
3
Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
4
Human Brain Tissue Bank & Laboratory, Semmelweis University, 1094 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Bobana Samardžija and Aristea Pavešić Radonja contributed equally and are co-first authors.
Academic Editor: Piotr Galecki
J. Pers. Med. 2021, 11(11), 1070; https://doi.org/10.3390/jpm11111070
Received: 6 September 2021 / Revised: 15 October 2021 / Accepted: 20 October 2021 / Published: 23 October 2021
(This article belongs to the Section Mechanisms of Diseases)
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. View Full-Text
Keywords: blood serum; major depressive disorder; insular cortex; mental illness; neuronal PAS protein 3 (NPAS3); post-mortem brain tissue; protein aggregation; proteinopathy; schizophrenia blood serum; major depressive disorder; insular cortex; mental illness; neuronal PAS protein 3 (NPAS3); post-mortem brain tissue; protein aggregation; proteinopathy; schizophrenia
Show Figures

Figure 1

MDPI and ACS Style

Samardžija, B.; Pavešić Radonja, A.; Zaharija, B.; Bergman, M.; Renner, É.; Palkovits, M.; Rubeša, G.; Bradshaw, N.J. Protein Aggregation of NPAS3, Implicated in Mental Illness, Is Not Limited to the V304I Mutation. J. Pers. Med. 2021, 11, 1070. https://doi.org/10.3390/jpm11111070

AMA Style

Samardžija B, Pavešić Radonja A, Zaharija B, Bergman M, Renner É, Palkovits M, Rubeša G, Bradshaw NJ. Protein Aggregation of NPAS3, Implicated in Mental Illness, Is Not Limited to the V304I Mutation. Journal of Personalized Medicine. 2021; 11(11):1070. https://doi.org/10.3390/jpm11111070

Chicago/Turabian Style

Samardžija, Bobana, Aristea Pavešić Radonja, Beti Zaharija, Mihaela Bergman, Éva Renner, Miklós Palkovits, Gordana Rubeša, and Nicholas J. Bradshaw. 2021. "Protein Aggregation of NPAS3, Implicated in Mental Illness, Is Not Limited to the V304I Mutation" Journal of Personalized Medicine 11, no. 11: 1070. https://doi.org/10.3390/jpm11111070

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop