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Pregled bibliografske jedinice broj: 1189871

Aggregation of “candidate proteins” for proteinopathy in mental illness


Bradshaw, Nicholas J.; Samardžija, Bobana; Zaharija, Beti; Pavešić Radonja, Aristea; Juković, Maja; Odorčić, Maja; Hart, Anja; Renner, Éva; Palkovits, Miklós; Rubeša, Gordana
Aggregation of “candidate proteins” for proteinopathy in mental illness // SIRS Florence, Italy 2022 Annual Congress Abstract Book
Firenca, Italija, 2022. str. 85-86 (pozvano predavanje, međunarodna recenzija, sažetak, znanstveni)


CROSBI ID: 1189871 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Aggregation of “candidate proteins” for proteinopathy in mental illness

Autori
Bradshaw, Nicholas J. ; Samardžija, Bobana ; Zaharija, Beti ; Pavešić Radonja, Aristea ; Juković, Maja ; Odorčić, Maja ; Hart, Anja ; Renner, Éva ; Palkovits, Miklós ; Rubeša, Gordana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
SIRS Florence, Italy 2022 Annual Congress Abstract Book / - , 2022, 85-86

Skup
Schizophrenia International Research Society 2022

Mjesto i datum
Firenca, Italija, 06.04.2022.-10.04.2022

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Cell biology ; Protein aggregation ; Proteinopathy ; Post mortem tissue

Sažetak
Background Genetic analysis of schizophrenia has made great progress in the last 15 years, identifying many loci that may influence its pathology. However, the existence of many risk variants of small individual effect, combined with rare variants, makes it difficult to identify individual protein targets for downstream study of this devastating psychiatric condition. To complement the genetic approach, we and others have been investigating potential disturbances of proteostasis in schizophrenia. Specifically, we hypothesize that there exist specific proteins that form insoluble protein aggregates in the brains of patients. These would be partially analogous to similar protein accumulations in the neurodegenerative disorders. This symposium will therefore open with a review and update of progress made to date in identifying proteins that aggregate in mental illness. Methods To date, most candidate aggregating proteins have been determined through the purification of the insoluble protein fraction of post mortem brain tissue (from patients with schizophrenia, bipolar disorder or major depressive disorder, plus controls). These have either been probed for the protein products of classic schizophrenia risk genes, or else subjected to proteomic analysis. Follow up work has largely consisted of expression of these proteins, in wild type, truncated or mutant forms, and examining their expression and effect in cultured cells or primary neurons, through a combination of immunofluorescent microscopy and biochemical techniques. Results To date, five proteins have been identified that may form insoluble aggregates in the brains of patients with schizophrenia, and in some instances also in the affective disorders. Of these, DISC1, dysbindin-1 and NPAS3 represent the protein products of classical, pre-GWAS, candidate genes, while CRMP1 and TRIOBP-1 were identified by proteomic approaches, and had not previously been associated with schizophrenia. All are expressed in the brain, and are variously implicated in neurodevelopment and/or synaptic function. Each protein has also been confirmed to be capable of forming aggregates in various experimental systems. We are studying the aggregation of these proteins. Notably, in most cases, their aggregation propensity is seen to be dependent on specific structural regions of the proteins. Such data allows further analysis of the mechanisms underlying their aggregation, and suggests routes ahead for their study. It is also notable that most of the proteins aggregate independently of each other, with only DISC1 showing a propensity to “co-aggregate” with other mental illness proteins in vivo and in vitro. Further clinical confirmation studies in patient and control samples are also ongoing. Conclusions While still in its infancy as a field, the existence of several insoluble or aggregated proteins in the brains of schizophrenia patients has now been confirmed. Further replication in a wider number of patients is now needed to determine whether this indeed represents a general biological feature of the condition. In parallel, cell and animal studies will help us to understand the pathophysiological consequences of such protein aggregates.

Izvorni jezik
Engleski

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



POVEZANOST RADA


Projekti:
HRZZ-IP-2018-01-9424 - Istraživanje shizofrenije kroz ekspresiju netopivih proteina (CandidIskren) (Bradshaw, Nicholas James, HRZZ - 2018-01) ( POIROT)
HRZZ-DOK-2018-09-5395 - Istraživanje shizofrenije kroz ekspresiju netopivih proteina (CandidIskren) (Bradshaw, Nicholas James, HRZZ - DOK-2018-09) ( POIROT)
HRZZ-DOK-2020-01-8580 - Istraživanje shizofrenije kroz ekspresiju netopivih proteina (CandidIskren) (Bradshaw, Nicholas James, HRZZ - DOK-2020-01) ( POIROT)
Ostalo-V-8151/17016 - Equipment subsidy / Gerätebehilfen (Bradshaw, Nicholas James, Ostalo ) ( POIROT)
Ostalo-3.4-1142747-HRV-IP - DISC1: Its Structure, Causes of Aggregation and Relevance to Disease (DISCARD collaboration) (Bradshaw, Nicholas James, Ostalo - Research Group Linkage Programme 10-2021) ( POIROT)

Ustanove:
Medicinski fakultet, Rijeka,
Sveučilište u Rijeci - Odjel za biotehnologiju

Citiraj ovu publikaciju:

Bradshaw, Nicholas J.; Samardžija, Bobana; Zaharija, Beti; Pavešić Radonja, Aristea; Juković, Maja; Odorčić, Maja; Hart, Anja; Renner, Éva; Palkovits, Miklós; Rubeša, Gordana
Aggregation of “candidate proteins” for proteinopathy in mental illness // SIRS Florence, Italy 2022 Annual Congress Abstract Book
Firenca, Italija, 2022. str. 85-86 (pozvano predavanje, međunarodna recenzija, sažetak, znanstveni)
Bradshaw, N., Samardžija, B., Zaharija, B., Pavešić Radonja, A., Juković, M., Odorčić, M., Hart, A., Renner, É., Palkovits, M. & Rubeša, G. (2022) Aggregation of “candidate proteins” for proteinopathy in mental illness. U: SIRS Florence, Italy 2022 Annual Congress Abstract Book.
@article{article, author = {Bradshaw, Nicholas J. and Samard\v{z}ija, Bobana and Zaharija, Beti and Pave\v{s}i\'{c} Radonja, Aristea and Jukovi\'{c}, Maja and Odor\v{c}i\'{c}, Maja and Hart, Anja and Renner, \'{E}va and Palkovits, Mikl\'{o}s and Rube\v{s}a, Gordana}, year = {2022}, pages = {85-86}, keywords = {Cell biology, Protein aggregation, Proteinopathy, Post mortem tissue}, title = {Aggregation of “candidate proteins” for proteinopathy in mental illness}, keyword = {Cell biology, Protein aggregation, Proteinopathy, Post mortem tissue}, publisherplace = {Firenca, Italija} }
@article{article, author = {Bradshaw, Nicholas J. and Samard\v{z}ija, Bobana and Zaharija, Beti and Pave\v{s}i\'{c} Radonja, Aristea and Jukovi\'{c}, Maja and Odor\v{c}i\'{c}, Maja and Hart, Anja and Renner, \'{E}va and Palkovits, Mikl\'{o}s and Rube\v{s}a, Gordana}, year = {2022}, pages = {85-86}, keywords = {Cell biology, Protein aggregation, Proteinopathy, Post mortem tissue}, title = {Aggregation of “candidate proteins” for proteinopathy in mental illness}, keyword = {Cell biology, Protein aggregation, Proteinopathy, Post mortem tissue}, publisherplace = {Firenca, Italija} }




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