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Apolipoprotein D takes center stage in the stress response of the aging and degenerative brain
被引:122
作者:

Dassati, Sarah
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Private Hosp Villa Melitta, Dept Neurol Rehabil, Bolzano, Italy Private Hosp Villa Melitta, Dept Neurol Rehabil, Bolzano, Italy

Waldner, Andreas
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Private Hosp Villa Melitta, Dept Neurol Rehabil, Bolzano, Italy Private Hosp Villa Melitta, Dept Neurol Rehabil, Bolzano, Italy

Schweigreiter, Ruediger
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h-index: 0
机构:
Med Univ Innsbruck, Bioctr, Div Neurobiochem, A-6020 Innsbruck, Austria Private Hosp Villa Melitta, Dept Neurol Rehabil, Bolzano, Italy
机构:
[1] Private Hosp Villa Melitta, Dept Neurol Rehabil, Bolzano, Italy
[2] Med Univ Innsbruck, Bioctr, Div Neurobiochem, A-6020 Innsbruck, Austria
基金:
奥地利科学基金会;
关键词:
Aging;
Alzheimer's disease;
Apolipoprotein;
Inflammation;
Lipid peroxidation;
Lipocalin;
Neurodegeneration;
Oxidative stress;
Reactive oxygen species;
Schizophrenia;
Stress response;
Stroke;
POLYUNSATURATED FATTY-ACIDS;
ALZHEIMERS-DISEASE BRAIN;
HUMAN CEREBROSPINAL-FLUID;
MESSENGER-RNA EXPRESSION;
OXIDATIVE STRESS;
PSYCHIATRIC-DISORDERS;
LIPID-PEROXIDATION;
NEURODEGENERATIVE DISEASES;
ARACHIDONIC-ACID;
LIFE-SPAN;
D O I:
10.1016/j.neurobiolaging.2014.01.148
中图分类号:
R592 [老年病学];
C [社会科学总论];
学科分类号:
03 ;
0303 ;
100203 ;
摘要:
Apolipoprotein D (ApoD) is an ancient member of the lipocalin family with a high degree of sequence conservation from insects to mammals. It is not structurally related to other major apolipoproteins and has been known as a small, soluble carrier protein of lipophilic molecules that is mostly expressed in neurons and glial cells within the central and peripheral nervous system. Recent data indicate that ApoD not only supplies cells with lipophilic molecules, but also controls the fate of these ligands by modulating their stability and oxidation status. Of particular interest is the binding of ApoD to arachidonic acid and its derivatives, which play a central role in healthy brain function. ApoD has been shown to act as a catalyst in the reduction of peroxidized eicosanoids and to attenuate lipid peroxidation in the brain. Manipulating its expression level in fruit flies and mice has demonstrated that ApoD has a favorable effect on both stress resistance and life span. The APOD gene is the gene that is upregulated the most in the aging human brain. Furthermore, ApoD levels in the nervous system are elevated in a large number of neurologic disorders including Alzheimer's disease, schizophrenia, and stroke. There is increasing evidence for a prominent neuroprotective role of ApoD because of its antioxidant and anti- inflammatory activity. ApoD emerges as an evolutionarily conserved anti-stress protein that is induced by oxidative stress and inflammation and may prove to be an effective therapeutic agent against a variety of neuropathologies, and even against aging. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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页码:1632 / 1642
页数:11
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