title: Cyclophilin D as a potential target for antioxidants in neurodegeneration: the X-ALD case.
abstract: 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.
authors.affiliation: Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, E-08908 Barcelona, Spain.
authors.forename: Jone
authors.initials: J
authors.lastname: López-Erauskin
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.forename: Elena
authors.initials: E
authors.lastname: Galea
authors.forename: Aurora
authors.initials: A
authors.lastname: Pujol
mesh_terms: D000326:Adrenoleukodystrophy / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D000975:Antioxidants; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase