Nalazite se na CroRIS probnoj okolini. Ovdje evidentirani podaci neće biti pohranjeni u Informacijskom sustavu znanosti RH. Ako je ovo greška, CroRIS produkcijskoj okolini moguće je pristupi putem poveznice www.croris.hr
izvor podataka: crosbi !

TRIOBP-1 aggreation and major mental illness (CROSBI ID 660018)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa

Bradshaw, Nicholas J. ; Marreiros, Rita ; Yerabham, Antony S. K. ; Korth, Carsten TRIOBP-1 aggreation and major mental illness // The 6. Croatian Neuroscience Congress with International Participation, Book of Abstract. 2017. str. 75-75

Podaci o odgovornosti

Bradshaw, Nicholas J. ; Marreiros, Rita ; Yerabham, Antony S. K. ; Korth, Carsten

engleski

TRIOBP-1 aggreation and major mental illness

Introduction: Schizophrenia is a devastating psychiatric condition with a strong genetic component. In common with other mental illnesses, however, the genetic basis of schizophrenia is highly complex, with many risk factors and a high degree of heterogeneity. One approach to bypass this complexity is to instead focus on proteins involved in these conditions, and thus provide insight into the mechanisms underlying major mental illness. Specifically, we have proposed that, in partial analogy with many neurodegenerative disorders, it may be possible to characterise subsets of mental illness patients through the presence of aggregated, insoluble deposits of specific proteins in the brain. Methods: In a hypothesis free approach to identify proteins which may aggregate specifically in the brains of major mental illness patients, the insoluble protein fraction was purified from samples of 15 brains from schizophrenia patients, pooled and used to immunize a mouse. Monoclonal antibodies were raised from this animal, and tested for clones that had the ability to specifically recognise the insoluble protein preparation from schizophrenia patients brains over an equivalent preparation derived from control individuals. One such antibody was isolated, and its antigen confirmed by proteomics. This protein was then studied through expression in primary neurons and neuronal-like cell lines, in order to investigate its propensity to aggregate and the mechanism by which this occurs. Results: Through the insoluble protein affinity technique, Trio-Binding Protein isoform-1 (TRIOBP-1) was confirmed to exist as an insoluble/aggregated species with the pooled brain samples from schizophrenia patients but not the controls samples. The TRIOBP-1 protein was found to aggregate both in its endogenous state and when over-expressed in a variety of systems, with enhanced aggregation occurring in neuroblastoma cells after they were induced to differentiate. Furthermore, this aggregation was found to be dependent on a short motif, currently narrowed to just 9 amino acids, within a central region of the protein that is required for its function in the polymerization of actin. This implies that a specific cellular process is likely involved in TRIOBP-1 aggregation. Conclusions: TRIOBP-1 is therefore one of a handful of proteins (also including DISC1, dysbindin and CRMP1) to be implicated as aggregating specifically in the brains of at least a subset of patients with major mental illness, and the first to be identified that was not previously implicated in psychiatric illness through prior genetic analysis. Through further analysis of this aggregation event it is hoped that insight can be gained into the cellular processes underlying major mental illnesses, as well as providing a potential new approach towards novel diagnosis and/or treatment of these conditions.

Mental illness ; Protein Aggregation ; Psychiatric Illness ; Schizophrenia

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o prilogu

75-75.

2017.

nije evidentirano

objavljeno

Podaci o matičnoj publikaciji

The 6. Croatian Neuroscience Congress with International Participation, Book of Abstract

Podaci o skupu

6. Croatian Neuroscience Congress with International Participation

poster

16.09.2017-18.09.2017

Osijek, Hrvatska

Povezanost rada

Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje), Biotehnologija, Interdisciplinarne biotehničke znanosti