Targeting mitochondrial dysfunction in neurodegenerative disease: Part I

被引：56

作者：

Burchell, Victoria S. ^{[1
]}

Gandhi, Sonia ^{[1
,2
]}

Deas, Emma ^{[1
]}

Wood, Nicholas W. ^{[1
]}

Abramov, Andrey Y.

Plun-Favreau, Helene

机构：

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

[2] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, London W12 0NN, England

来源：

EXPERT OPINION ON THERAPEUTIC TARGETS | 2010年 / 14卷 / 04期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

AMYLOID BETA-PROTEIN; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; THERAPEUTIC TARGET; COENZYME Q(10); DOUBLE-BLIND; CREATINE SUPPLEMENTATION; FRIEDREICH ATAXIA;

D O I：

10.1517/14728221003652489

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Importance of the field: The socioeconomic burden of an aging population has accelerated the urgency of novel therapeutic strategies for neurodegenerative disease. One possible approach is to target mitochondrial dysfunction, which has been implicated in the pathogenesis of numerous neurodegenerative disorders. Areas covered in this review: This review examines the role of mitochondrial defects in aging and neurodegenerative disease, ranging from common diseases such as Alzheimer's and Parkinson's disease to rare familial disorders such as the spinocerebellar ataxias. The review is provided in two parts; in this first part, we discuss the mitochondrial defects that have been most extensively researched: oxidative stress; bioenergetic dysfunction and calcium deregulation. What the reader will gain: This review provides a comprehensive examination of mitochondrial defects observed in numerous neurodegenerative disorders, discussing therapies that have reached clinical trials and considering potential novel therapeutic strategies to target mitochondrial dysfunction. Take home message: This is an important area of clinical research, with several novel therapeutics already in clinical trials and many more in preclinical stages. In part II of this review we will focus on possible novel approaches, looking at mitochondrial defects which have more recently been linked to neurodegeneration.

引用

页码：369 / 385

页数：17

共 124 条

[1] Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial [J].

Aarsland, Dag ;

Ballard, Clive ;

Walker, Zuzana ;

Bostrom, Fredrik ;

Alves, Guido ;

Kossakowski, Katja ;

Leroi, Iracema ;

Pozo-Rodriguez, Francisco ;

Minthon, Lennart ;

Londos, Elisabet .

LANCET NEUROLOGY, 2009, 8 (07) :613-618

[2] Mechanisms underlying the loss of mitochondrial membrane potential in glutamate excitotoxicity [J].

Abramov, Andrey Y. ;

Duchen, Michael R. .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2008, 1777 (7-8) :953-964

[3] Impaired mitochondrial bioenergetics determines glutamate-induced delayed calcium deregulation in neurons [J].

Abramov, Andrey Y. ;

Duchen, Michael R. .

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2010, 1800 (03) :297-304

[4] 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

[5]

Abramov AY, 2003, J NEUROSCI, V23, P5088

[6] The expression of creatine kinase isoenzymes in neocortex of patients with neurodegenerative disorders: Alzheimer's and Pick's disease [J].

Aksenov, MY ;

Aksenova, MV ;

Payne, RM ;

Smith, CD ;

Markesbery, WR ;

Carney, JM .

EXPERIMENTAL NEUROLOGY, 1997, 146 (02) :458-465

[7] Frontal lobe dysfunction in progressive supranuclear palsy: Evidence for oxidative stress and mitochondrial impairment [J].

Albers, DS ;

Augood, SJ ;

Park, LCH ;

Browne, SE ;

Martin, DM ;

Adamson, J ;

Hutton, M ;

Standaert, DG ;

Vonsattel, JPG ;

Gibson, GE ;

Beal, MF .

JOURNAL OF NEUROCHEMISTRY, 2000, 74 (02) :878-881

[8] DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase [J].

Andres-Mateos, Eva ;

Perier, Celine ;

Zhang, Li ;

Blanchard-Fillion, Beatrice ;

Greco, Todd M. ;

Thomas, Bobby ;

Ko, Han Seok ;

Sasaki, Masayuki ;

Ischiropoulos, Harry ;

Przedborski, Serge ;

Dawson, Ted M. ;

Dawson, Valina L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (37) :14807-14812

[9] ALZHEIMER-DISEASE AMYLOID BETA-PROTEIN FORMS CALCIUM CHANNELS IN BILAYER-MEMBRANES - BLOCKADE BY TROMETHAMINE AND ALUMINUM [J].

ARISPE, N ;

ROJAS, E ;

POLLARD, HB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (02) :567-571

[10] Mitochondria, oxidants, and aging [J].

Balaban, RS ;

Nemoto, S ;

Finkel, T .

CELL, 2005, 120 (04) :483-495

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