J 2021

Ferroptosis and its potential role in the physiopathology of Parkinson's Disease

MAHONEY-SANCHEZ, L., H. BOUCHAOUI, S. AYTON, D. DEVOS, JA. DUCE et. al.

Základní údaje

Originální název

Ferroptosis and its potential role in the physiopathology of Parkinson's Disease

Autoři

MAHONEY-SANCHEZ, L. (garant), H. BOUCHAOUI, S. AYTON, D. DEVOS, JA. DUCE a JC. DEVEDJIAN

Vydání

PROGRESS IN NEUROBIOLOGY, OXFORD, PERGAMON-ELSEVIER SCIENCE LTD, 2021, 0301-0082

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30230 Other clinical medicine subjects

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 10.885

Kód RIV

RIV/00216224:14110/21:00124114

Organizační jednotka

Lékařská fakulta

UT WoS

000604785900006

Klíčová slova česky

Parkinson's Disease; Non apoptotic cell death; Ferroptosis; Iron metabolism; Oxidative stress; Lipid peroxidation; Alpha synuclein

Klíčová slova anglicky

Parkinson's Disease; Non apoptotic cell death; Ferroptosis; Iron metabolism; Oxidative stress; Lipid peroxidation; Alpha synuclein

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 3. 5. 2022 08:49, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

90128, velká výzkumná infrastruktura
Název: CZECRIN III