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

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.

Basic information

Original name

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

Authors

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

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30230 Other clinical medicine subjects

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

FAIRPARK II

Impact factor

Impact factor: 10.885

RIV identification code

RIV/00216224:14110/21:00124114

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.pneurobio.2020.101890

UT WoS

000604785900006

Keywords (in Czech)

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

Keywords in English

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

Abstract

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.

Links

90128, large research infrastructures

Name: CZECRIN III

Citovat

MAHONEY-SANCHEZ, L., H. BOUCHAOUI, S. AYTON, D. DEVOS, JA. DUCE and JC. DEVEDJIAN. Ferroptosis and its potential role in the physiopathology of Parkinson's Disease. PROGRESS IN NEUROBIOLOGY. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2021, vol. 196, January 2021, p. 1-12. ISSN 0301-0082. Available from: https://dx.doi.org/10.1016/j.pneurobio.2020.101890.

@article{1833143,
   author = {MahoneyandSanchez, L. and Bouchaoui, H. and Ayton, S. and Devos, D. and Duce, JA. and Devedjian, JC.},
   article_location = {OXFORD},
   article_number = {January 2021},
   doi = {http://dx.doi.org/10.1016/j.pneurobio.2020.101890},
   keywords = {Parkinson's Disease; Non apoptotic cell death; Ferroptosis; Iron metabolism; Oxidative stress; Lipid peroxidation; Alpha synuclein},
   language = {eng},
   issn = {0301-0082},
   journal = {PROGRESS IN NEUROBIOLOGY},
   note = {FairPark II},
   title = {Ferroptosis and its potential role in the physiopathology of Parkinson's Disease},
   url = {https://www.sciencedirect.com/science/article/pii/S0301008220301453?via%3Dihub},
   volume = {196},
   year = {2021}
}

TY  - JOUR
ID  - 1833143
AU  - Mahoney-Sanchez, L. - Bouchaoui, H. - Ayton, S. - Devos, D. - Duce, JA. - Devedjian, JC.
PY  - 2021
TI  - Ferroptosis and its potential role in the physiopathology of Parkinson's Disease
JF  - PROGRESS IN NEUROBIOLOGY
VL  - 196
IS  - January 2021
SP  - 1-12
EP  - 1-12
PB  - PERGAMON-ELSEVIER SCIENCE LTD
SN  - 03010082
N1  - FairPark II
KW  - Parkinson's Disease
KW  - Non apoptotic cell death
KW  - Ferroptosis
KW  - Iron metabolism
KW  - Oxidative stress
KW  - Lipid peroxidation
KW  - Alpha synuclein
UR  - https://www.sciencedirect.com/science/article/pii/S0301008220301453?via%3Dihub
N2  - 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.
ER  -

MAHONEY-SANCHEZ, L., H. BOUCHAOUI, S. AYTON, D. DEVOS, JA. DUCE and JC. DEVEDJIAN. Ferroptosis and its potential role in the physiopathology of Parkinson's Disease. \textit{PROGRESS IN NEUROBIOLOGY}. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2021, vol.~196, January 2021, p.~1-12. ISSN~0301-0082. Available from: https://dx.doi.org/10.1016/j.pneurobio.2020.101890.

Detailed Information on Publication Record