MECHANISM OF NEUROPROTECTION OF MELATONIN AGAINST BETA-AMYLOID NEUROTOXICITY

被引：49

作者：

Ionov, M. ^{[2
]}

Burchell, V. ^{[1
]}

Klajnert, B. ^{[2
]}

Bryszewska, M. ^{[2
]}

Abramov, A. Y. ^{[1
]}

机构：

[1] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England

[2] Univ Lodz, Dept Gen Biophys, PL-90237 Lodz, Poland

来源：

NEUROSCIENCE | 2011年 / 180卷

关键词：

beta-amyloid; melatonin; mitochondria; Ca2+; reactive oxygen species; astrocytes; ALZHEIMERS-DISEASE; MITOCHONDRIAL DYSFUNCTION; OXIDATIVE STRESS; NADPH OXIDASE; PEPTIDE; CALCIUM; AGGREGATION; ASTROCYTES; DEATH; NEURONS;

D O I：

10.1016/j.neuroscience.2011.02.045

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The main component of senile plaques in Alzheimer's disease (AD), aggregated amyloid beta peptide (beta A), is neurotoxic and implicated in AD pathology. Melatonin is a hormone secreted from the pineal gland, levels of which are decreased in aging, particularly in AD subjects. This hormone is known to possess neuroprotective properties against beta A toxicity in vivo, but the mechanism of protection remains controversial. In cultures of mixed neurones and astrocytes, we find that melatonin is protective against neuronal and astrocytic death induced by aggregated full length beta A 1-40 and the fragments beta A 25-40 and beta A 1-28. Melatonin had no effect on the process of fibrillation of beta A and did not alter beta A-induced calcium signalling in astrocytes, but did significantly reduce the rate of beta A-induced reactive oxygen species production and also protected astrocytes against the mitochondria! depolarisation. Thus, scavenging of reactive oxygen species by melatonin appears to be the primary effect of melatonin in protecting neurones and astrocytes against beta A toxicity. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：229 / 237

页数：9

共 29 条

[1]

Abramov AY, 2008, BIOL MEMBRANY, V25, P11

[2] Targeted polyphosphatase expression alters mitochondrial metabolism and inhibits calcium-dependent cell death [J].

Abramov, Andrey Y. ;

Fraley, Cresson ;

Diao, Catherine T. ;

Winkfein, Robert ;

Colicos, Michael A. ;

Duchen, Michael R. ;

French, Robert J. ;

Pavlov, Evgeny .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (46) :18091-18096

[3] The role of an astrocytic NADPH oxidase in the neurotoxicity of amyloid beta peptides [J].

Abramov, AY ;

Duchen, MR .

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2005, 360 (1464) :2309-2314

[4] Calcium signals induced by amylold β peptide and their consequences in neurons and astrocytes in culture [J].

Abramov, AY ;

Canevari, L ;

Duchen, MR .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2004, 1742 (1-3) :81-87

[5] β-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase [J].

Abramov, AY ;

Canevari, L ;

Duchen, MR .

JOURNAL OF NEUROSCIENCE, 2004, 24 (02) :565-575

[6]

Abramov AY, 2003, J NEUROSCI, V23, P5088

[7] GIANT MULTILEVEL CATION CHANNELS FORMED BY ALZHEIMER-DISEASE AMYLOID BETA-PROTEIN [A-BETA-P-(1-40)] IN BILAYER-MEMBRANES [J].

ARISPE, N ;

POLLARD, HB ;

ROJAS, E .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (22) :10573-10577

[8] HYDROGEN-PEROXIDE MEDIATES AMYLOID-BETA PROTEIN TOXICITY [J].

BEHL, C ;

DAVIS, JB ;

LESLEY, R ;

SCHUBERT, D .

CELL, 1994, 77 (06) :817-827

[9] Conversion of non-fibrillar β-sheet oligomers into amyloid fibrils in Alzheimer's disease amyloid peptide aggregation [J].

Benseny-Cases, Nuria ;

Cocera, Mercedes ;

Cladera, Josep .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 361 (04) :916-921

[10] Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease [J].

Bezprozvanny, Ilya ;

Mattson, Mark P. .

TRENDS IN NEUROSCIENCES, 2008, 31 (09) :454-463

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