RNase T1 Refolding Assay for Determining Mitochondrial Cyclophilin D Activity: A Novel In Vitro Method Applicable in Drug Research and Discovery

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F20%3A50016740" target="_blank" >RIV/62690094:18470/20:50016740 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/20:10418150

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.biochem.9b01025?ref=pdf" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.biochem.9b01025?ref=pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.biochem.9b01025" target="_blank" >10.1021/acs.biochem.9b01025</a>

Jazyk výsledku

angličtina

Název v původním jazyce

RNase T1 Refolding Assay for Determining Mitochondrial Cyclophilin D Activity: A Novel In Vitro Method Applicable in Drug Research and Discovery

Popis výsledku v původním jazyce

Human cyclophilin D is a mitochondrial peptidyl-prolyl isomerase that plays a role in regulating the opening of the mitochondrial permeability transition pore. It is considered a viable and promising molecular target for the treatment of diseases for which disease development is associated with pore opening, e.g., Alzheimer&apos;s disease or ischemia/reperfusion injury. Currently available and widely used in vitro methods based on Kofron&apos;s assay for determining cyclophilin D activity suffer from serious drawbacks and limitations. In this study, a completely novel approach for an in vitro assay of cyclophilin D activity using RNase T1 refolding is introduced. The method is simple and is more in line with the presumed physiological role of cydophilin D in protein folding than Kofron&apos;s assay, which relies on a peptide substrate. The method is applicable for identifying novel inhibitors of cyclophilin D as potential drugs for the treatment of the diseases mentioned above. Moreover, the description of CypD activity in the in vitro RNase T1 refolding assay reveals new possibilities for investigating the role of cyclophilin D in protein folding in cells and may lead to a better understanding of its pathological and physiological roles.

Název v anglickém jazyce

RNase T1 Refolding Assay for Determining Mitochondrial Cyclophilin D Activity: A Novel In Vitro Method Applicable in Drug Research and Discovery

Popis výsledku anglicky

Human cyclophilin D is a mitochondrial peptidyl-prolyl isomerase that plays a role in regulating the opening of the mitochondrial permeability transition pore. It is considered a viable and promising molecular target for the treatment of diseases for which disease development is associated with pore opening, e.g., Alzheimer&apos;s disease or ischemia/reperfusion injury. Currently available and widely used in vitro methods based on Kofron&apos;s assay for determining cyclophilin D activity suffer from serious drawbacks and limitations. In this study, a completely novel approach for an in vitro assay of cyclophilin D activity using RNase T1 refolding is introduced. The method is simple and is more in line with the presumed physiological role of cydophilin D in protein folding than Kofron&apos;s assay, which relies on a peptide substrate. The method is applicable for identifying novel inhibitors of cyclophilin D as potential drugs for the treatment of the diseases mentioned above. Moreover, the description of CypD activity in the in vitro RNase T1 refolding assay reveals new possibilities for investigating the role of cyclophilin D in protein folding in cells and may lead to a better understanding of its pathological and physiological roles.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EF18_069%2F0010054" target="_blank" >EF18_069/0010054: IT4Neuro(degeneration)</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biochemistry

ISSN

0006-2960

e-ISSN

—

Svazek periodika

59

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

1680-1687

Kód UT WoS článku

000530650400010

EID výsledku v databázi Scopus

2-s2.0-85084270684