Ferroptosis and its potential role in the physiopathology of Parkinson's Disease
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F21%3A00124114" target="_blank" >RIV/00216224:14110/21:00124114 - isvavai.cz</a>
Výsledek na webu
<a href="https://www.sciencedirect.com/science/article/pii/S0301008220301453?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0301008220301453?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.pneurobio.2020.101890" target="_blank" >10.1016/j.pneurobio.2020.101890</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Ferroptosis and its potential role in the physiopathology of Parkinson's Disease
Popis výsledku v původním jazyce
Parkinson's Disease (PD) is a common and progressive neurodegenerative disorder characterised by motor impairments as well as non-motor symptoms. While dopamine-based therapies are effective in fighting the symptoms in the early stages of the disease, a lack of neuroprotective drugs means that the disease continues to progress. Along with the traditionally recognised pathological hallmarks of dopaminergic neuronal death and intracellular a-synuclein (alpha-syn) depositions, iron accumulation, elevated oxidative stress and lipid peroxidation damage are further conspicuous features of PD pathophysiology. However, the underlying mechanisms linking these pathological hallmarks with neurodegeneration still remain unclear. Ferroptosis, a regulated iron dependent cell death pathway involving a lethal accumulation of lipid peroxides, shares several features with PD pathophysiology. Interestingly, alpha-syn has been functionally linked with the metabolism of both iron and lipid, suggesting a possible interplay between dysregulated alpha-syn and other PD pathological hallmarks related to ferroptosis. This review will address the importance for understanding these disease mechanisms that could be targeted therapeutically. Anti-ferroptosis molecules are neuroprotective in PD animal models and the anti-ferroptotic iron chelator, deferiprone, slowed disease progression and improved motor function in two independent clinical trials for PD. An ongoing larger multi-centre phase 2 clinical trial will confirm the therapeutic potential of deferiprone and the relevance of ferroptosis in PD. This review addresses the known pathological features of PD in relation to the ferroptosis pathway with therapeutic implications of targeting this cell death pathway.
Název v anglickém jazyce
Ferroptosis and its potential role in the physiopathology of Parkinson's Disease
Popis výsledku anglicky
Parkinson's Disease (PD) is a common and progressive neurodegenerative disorder characterised by motor impairments as well as non-motor symptoms. While dopamine-based therapies are effective in fighting the symptoms in the early stages of the disease, a lack of neuroprotective drugs means that the disease continues to progress. Along with the traditionally recognised pathological hallmarks of dopaminergic neuronal death and intracellular a-synuclein (alpha-syn) depositions, iron accumulation, elevated oxidative stress and lipid peroxidation damage are further conspicuous features of PD pathophysiology. However, the underlying mechanisms linking these pathological hallmarks with neurodegeneration still remain unclear. Ferroptosis, a regulated iron dependent cell death pathway involving a lethal accumulation of lipid peroxides, shares several features with PD pathophysiology. Interestingly, alpha-syn has been functionally linked with the metabolism of both iron and lipid, suggesting a possible interplay between dysregulated alpha-syn and other PD pathological hallmarks related to ferroptosis. This review will address the importance for understanding these disease mechanisms that could be targeted therapeutically. Anti-ferroptosis molecules are neuroprotective in PD animal models and the anti-ferroptotic iron chelator, deferiprone, slowed disease progression and improved motor function in two independent clinical trials for PD. An ongoing larger multi-centre phase 2 clinical trial will confirm the therapeutic potential of deferiprone and the relevance of ferroptosis in PD. This review addresses the known pathological features of PD in relation to the ferroptosis pathway with therapeutic implications of targeting this cell death pathway.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30230 - Other clinical medicine subjects
Návaznosti výsledku
Projekt
—
Návaznosti
—
Ostatní
Rok uplatnění
2021
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
PROGRESS IN NEUROBIOLOGY
ISSN
0301-0082
e-ISSN
1873-5118
Svazek periodika
196
Číslo periodika v rámci svazku
January 2021
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
12
Strana od-do
1-12
Kód UT WoS článku
000604785900006
EID výsledku v databázi Scopus
2-s2.0-85089005401