Naslov
Protein aggregation and insolubility as a biologial component of chronic mental illness

Autori
Bradshaw, Nicholas J. ; Gvoić, Ines ; Odorčić, Maja ; Zaharija, Beti ; Rubeša, Gordana ; Pavešić Radonja, Aristea

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

Izvornik
Psychiatria Danubina (Volume 30, Supplement 1) / - Zagreb : Danubian Psychiatic Association, 2018, S32-S33

Skup
4. hrvatsko – ruski kongres duhovne psihijatrije s međunarodnim sudjelovanjem = 4th International symposium croatian-russian psychiatric congress

Mjesto i datum
Opatija, Hrvatska, 13.04.2018. - 15.04.2018

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Recenziran

Ključne riječi
Protein aggregation ; Schizophrenia ; Depression ; Mental Illness

Sažetak
Major mental illnesses such as schizophrenia and chronic depression are acknowledged to have biological underpinnings, however intense analysis has demonstrated their genetic background to be extremely complex, with very few obvious targets for future therapeutic approaches. Major neurodegenerative conditions, such as Alzheimer’s disease, Parkinson’s disease or amyotrophic lateral sclerosis, also have complex genetic backgrounds, but can nevertheless be characterised by the presence of insoluble aggregates of a very few specific proteins in the brain. These proteins are often toxic, and contribute to the worsening of patients’ symptoms with time. Taking inspiration from this, we and others have begun investigating the existence of similar protein aggregates in the brains of patients with chronic mental illnesses. Through biochemical approaches based on isolating the insoluble protein fractions of patient brain samples, five proteins have now been identified with the potential to form aggregates in major mental illness. Three of these (DISC1, dysbindin-1 and NPAS3) were investigated as they are encoded for by previously described genetic risk factors. The remaining two (CRMP1 and TRIOBP-1) were identified through hypothesis-free proteomics approaches, and represent proteins which had not been previously associated with mental illness. All five have the potential to form aggregates in the brain of schizophrenia patients, with some also been implicated in this way in bipolar disorder and major depression. We are now embarking on a comprehensive program to characterise these five proteins and the role in which their aggregation plays in major mental illness. This will occur principally at the cell biology level: determining the mechanisms through which aggregates form and their consequences on neuronal development and function. A particular focus will be on interactions between the proteins, and the extent to which aggregation of one protein can affect the aggregation propensity of the others. In parallel, the five proteins will be studied in the blood of patients with schizophrenia, in order to determine their viability as diagnostic markers. A major hurdle in the development of biological diagnoses and rational therapeutics for major mental illness is the lack of well- characterised molecular targets, a direct effect of their genetic complexity. By bypassing genes and instead focussing on downstream proteins, it is hoped that the development of such new techniques can be greatly accelerated.

Izvorni jezik
Engleski

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

POVEZANOST RADA