Promethazine protects against 3-nitropropionic acid-induced neurotoxicity

被引：5

作者：

Cleren, Carine ^{[1
]}

Calingasan, Noel Y. ^{[1
]}

Starkov, Anatoly ^{[1
]}

Jacquard, Carine ^{[2
,3
]}

Chen, Junya ^{[1
]}

Brouillet, Emmanuel ^{[2
,3
]}

Beal, M. Flint ^{[1
]}

机构：

[1] Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Neurol & Neurosci, New York, NY 10065 USA

[2] CEA, DSV, I2BM, Mol Imaging Res Ctr MIRCen, F-92265 Fontenay Aux Roses, France

[3] CEA, CNRS, URA 2210, F-92265 Fontenay Aux Roses, France

来源：

NEUROCHEMISTRY INTERNATIONAL | 2010年 / 56卷 / 02期

关键词：

Huntington; Neurotoxicity; Neuroprotection; Apoptosis; Calbindin; Succinate dehydrogenase; Mitochondria; STRIATAL DEGENERATION; MITOCHONDRIAL TOXIN; HUNTINGTONS-DISEASE; PERMEABILITY TRANSITION; IN-VIVO; MPTP; CALPAIN; VULNERABILITY; MALONATE; DEFECTS;

D O I：

10.1016/j.neuint.2009.10.006

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：

Promethazine (PMZ), an FDA-approved anti histaminergic drug, was identified as a potentially neuroprotective compound in a NINDS screening program. It was shown to protect against ischemia in mice, to delay disease onset in a mouse model of amyotrophic lateral sclerosis and to inhibit Ca2+-induced mitochondrial permeability transition in rat liver mitochondria. We investigated whether PMZ could protect against the neurotoxic effects induced by 3-nitropropionic acid (3-NP), an inhibitor of the succinate dehydrogenase, used to model Huntington's disease (HD) in rats. Lewis rats receiving chronic subcutaneous infusion of 3-NP were treated with PMZ. The findings indicate that chronic PMZ treatment significantly reduced 3-NP-induced striatal lesion volume, loss of GABAergic neurons and number of apoptotic cells in the striatum. PMZ showed a strong neuroprotective effect against 3-NP toxicity in vivo. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：208 / 212

页数：5

共 33 条

[1] 3-NITROPROPIONATE, TOXIC SUBSTANCE OF INDIGOFERA, IS A SUICIDE INACTIVATOR OF SUCCINATE-DEHYDROGENASE - (RAT-LIVER MITOCHONDRIA CARBANION-N-5 FLAVIN ADDUCTS 2-PROTON ABSTRACTION MECHANISM) [J].