Cyclophilin D as a potential target for antioxidants in neurodegeneration: the X-ALD case

被引：7

作者：

Lopez-Erauskin, Jone ^{[1
,2
,4
]}

Ferrer, Isidre ^{[2
,4
]}

Galea, Elena ^{[3
,5
]}

Pujol, Aurora ^{[1
,2
,3
]}

机构：

[1] Lhosp Llobregat, Neurometabol Dis Lab Bellvitge Biomed Res Inst ID, E-08908 Barcelona, Spain

[2] Lhosp Llobregat, IDIBELL Hosp Univ Bellvitge, Bellvitge Biomed Res Inst, Inst Neuropathol,Pathol Anat Serv, E-08908 Barcelona, Spain

[3] Catalan Inst Res & Adv Studies ICREA, E-08010 Barcelona, Spain

[4] Lhosp Llobregat, Ctr Biomed Res Rare Dis CIBERER U759, E-8908 Barcelona, Spain

[5] Univ Autonoma Barcelona, Inst Neurosci, E-08193 Barcelona, Spain

来源：

BIOLOGICAL CHEMISTRY | 2013年 / 394卷 / 05期

关键词：

cyclophilin D; neurodegeneration; mitochondrial permeability transition pore; oxidative stress; very long chain fatty acids; X-linked adrenoleukodystrophy; MITOCHONDRIAL PERMEABILITY TRANSITION; CHAIN FATTY-ACIDS; LINKED ADRENOLEUKODYSTROPHY GENE; PEROXISOMAL ABCD2 TRANSPORTER; OXIDATIVE STRESS; MOUSE MODEL; AXONAL DEGENERATION; PARKINSONS-DISEASE; HEART-MITOCHONDRIA; CELL-DEATH;

D O I：

10.1515/hsz-2012-0323

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

X-linked adrenoleukodystrophy (X-ALD) is a severe inherited neurodegenerative disorder characterized by adrenal insufficiency and graded damage in the nervous system. Loss of function of the peroxisomal ABCD1 fatty-acid transporter, resulting in the accumulation of very long-chain fatty acids in organs and plasma, is the genetic cause. Treatment with a combination of antioxidants halts the axonal degeneration and locomotor impairment displayed by the animal model of X-ALD, and is a proof of concept that oxidative stress contributes to axonal damage. New evidence demonstrates that metabolic failure and the opening of the mitochondrial permeability transition pore orchestrated by cyclophilin D underlies oxidative stress-induced axonal degeneration. Thus, cyclophilin D could serve as a therapeutic target for the treatment of X-ALD and cyclophilin D-dependent neurodegenerative and non-neurodegenerative diseases.

引用

页码：621 / 629

页数：9

共 73 条

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