The roles of free radicals in amyotrophic lateral sclerosis

被引：34

作者：

Liu, DX ^{[1
]}

机构：

[1] UNIV TEXAS, MED BRANCH, INST MARINE BIOMED, GALVESTON, TX 77550 USA

来源：

JOURNAL OF MOLECULAR NEUROSCIENCE | 1996年 / 7卷 / 03期

关键词：

amyotrophic lateral sclerosis; Cu; Zn superoxide dismutase; free radicals; glutamate toxicity; motor neuron degeneration; oxidative damage; programmed neuron death;

D O I：

10.1007/BF02736837

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：

The mutations of the Cu,Zn superoxide dismutase (Cu,Zn-SOD) gene observed in amyotrophic lateral sclerosis (ALS) patients suggest that free radicals play a role in this fatal disease. Free radicals trigger oxidative damage to proteins, membrane lipids, and DNA, thereby destroying neurons. Mutations of the SOD gene may reduce its superoxide dismutase activity, thereby elevating free radical levels. In addition, the mutant SOD protein may function as a peroxidase to oxidize cellular components, and it may also react with peroxynitrite-a product of the reaction between superoxide and nitric oxide-to ultimately form nitrate proteins. The selective degeneration of motor neurons in ALS may be caused by the high level of Cu,Zn-SOD present in and the large number of glutamatergic synapses projecting to these neurons. Free radical-triggered and age-accumulated oxidation may modify the program controlling motor neuron death, thereby initiating apoptosis of motor neurons in young adults.

引用

页码：159 / 167

页数：9

共 100 条

[21] ALTERATIONS OF MEMBRANE INTEGRITY AND CELLULAR-CONSTITUENTS BY ARACHIDONIC-ACID IN NEURO-BLASTOMA AND GLIOMA-CELLS [J].

CHAN, PH ;

FISHMAN, RA .

BRAIN RESEARCH, 1982, 248 (01) :151-157

[22] OXIDATIVE STRESS, GLUTAMATE, AND NEURODEGENERATIVE DISORDERS [J].

COYLE, JT ;

PUTTFARCKEN, P .

SCIENCE, 1993, 262 (5134) :689-695

[23] OXIDATIVE DAMAGE TO HUMAN PLASMA-PROTEINS BY OZONE [J].

CROSS, CE ;

REZNICK, AZ ;

PACKER, L ;

DAVIS, PA ;

SUZUKI, YJ ;

HALLIWELL, B .

FREE RADICAL RESEARCH COMMUNICATIONS, 1992, 15 (06) :347-352

[24] A NOVEL NEURONAL MESSENGER MOLECULE IN BRAIN - THE FREE-RADICAL, NITRIC-OXIDE [J].

DAWSON, TM ;

DAWSON, VL ;

SNYDER, SH .

ANNALS OF NEUROLOGY, 1992, 32 (03) :297-311

[25] NITRIC-OXIDE MEDIATES GLUTAMATE NEUROTOXICITY IN PRIMARY CORTICAL CULTURES [J].

DAWSON, VL ;

DAWSON, TM ;

LONDON, ED ;

BREDT, DS ;

SNYDER, SH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (14) :6368-6371

[26] AMYOTROPHIC-LATERAL-SCLEROSIS AND STRUCTURAL DEFECTS IN CU,ZN SUPEROXIDE-DISMUTASE [J].

DENG, HX ;

HENTATI, A ;

TAINER, JA ;

IQBAL, Z ;

CAYABYAB, A ;

HUNG, WY ;

GETZOFF, ED ;

HU, P ;

HERZFELDT, B ;

ROOS, RP ;

WARNER, C ;

DENG, G ;

SORIANO, E ;

SMYTH, C ;

PARGE, HE ;

AHMED, A ;

ROSES, AD ;

HALLEWELL, RA ;

PERICAKVANCE, MA ;

SIDDIQUE, T .

SCIENCE, 1993, 261 (5124) :1047-1051

[27] OVERPRODUCTION OF HUMAN CU/ZN-SUPEROXIDE DISMUTASE IN TRANSFECTED CELLS - EXTENUATION OF PARAQUAT-MEDIATED CYTOTOXICITY AND ENHANCEMENT OF LIPID-PEROXIDATION [J].

ELROYSTEIN, O ;

BERNSTEIN, Y ;

GRONER, Y .

EMBO JOURNAL, 1986, 5 (03) :615-622

[28] FREE-RADICAL DAMAGE TO PROTEIN AND DNA - MECHANISMS INVOLVED AND RELEVANT OBSERVATIONS ON BRAIN UNDERGOING OXIDATIVE STRESS [J].

FLOYD, RA ;

CARNEY, JM .

ANNALS OF NEUROLOGY, 1992, 32 :S22-S27

[29] FORMATION OF 8-HYDROXYDEOXYGUANOSINE, HYDROXYL FREE-RADICAL ADDUCT OF DNA IN GRANULOCYTES EXPOSED TO THE TUMOR PROMOTER, TETRADECONYLPHORBOLACETATE [J].

FLOYD, RA ;

WATSON, JJ ;

HARRIS, J ;

WEST, M ;

WONG, PK .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 137 (02) :841-846

[30] HYDROXYL FREE-RADICAL MEDIATED FORMATION OF 8-HYDROXYGUANINE IN ISOLATED DNA [J].

FLOYD, RA ;

WEST, MS ;

ENEFF, KL ;

HOGSETT, WE ;

TINGEY, DT .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1988, 262 (01) :266-272

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