Are mitochondria critical in the pathogenesis of Alzheimer's disease?

被引:247
作者
Reddy, PH
Beal, MF
机构
[1] Oregon Hlth & Sci Univ, Neurogenet Lab, Neurol Sci Inst, Beaverton, OR 97006 USA
[2] Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA
关键词
mitochondria; mitochondrial mutation; mitochondrial gene expression; oxidative damage; sporadic Alzheimer's disease; in vitro study; peripheral cell; transgenic mice;
D O I
10.1016/j.brainresrev.2005.03.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
This review summarizes recent findings that suggest a causal connection between mitochondrial abnormalities and sporadic Alzheimer's disease (AD). Genetic causes of AD are known only for a small proportion of familial AD patients, but for a majority of sporadic AD patients, genetic causal factors are still unknown. Currently, there are no early detectable biomarkers for sporadic AD, and there is a lack of understanding of the pathophysiology of the disease. Findings from recent genetic studies of AD pathogenesis suggest that mitochondrial defects may play an important role in sporadic AD progression, and that mitochondrial abnormalities and oxidative damage may play a significant role in the progression of familial AD. Findings from biochemical studies, in vitro studies, gene expression studies, and animal model studies of AD are reviewed, and the possible contribution of mitochondrial mutations to late-onset sporadic AD is discussed. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:618 / 632
页数:15
相关论文
共 160 条
  • [1] ISOLATION, CHARACTERIZATION, AND MAPPING OF GENE ENCODING DIHYDROLIPOYL SUCCINYLTRANSFERASE (E2K) OF HUMAN ALPHA-KETOGLUTARATE DEHYDROGENASE COMPLEX
    ALI, G
    WASCO, W
    CAI, XG
    SZABO, P
    SHEU, KFR
    COOPER, AJL
    GASTON, SM
    GUSELLA, JF
    TANZI, RE
    BLASS, JP
    [J]. SOMATIC CELL AND MOLECULAR GENETICS, 1994, 20 (02) : 99 - 105
  • [2] Mitochondria and vascular lesions as a central target for the development of Alzheimer's disease and Alzheimer disease-like pathology in transgenic mice
    Aliev, G
    Seyidova, D
    Lamb, BT
    Obrenovich, ME
    Siedlak, SL
    Vinters, HV
    Friedland, RP
    LaManna, JC
    Smith, MA
    Perry, G
    [J]. NEUROLOGICAL RESEARCH, 2003, 25 (06) : 665 - 674
  • [3] Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells
    Anandatheerthavarada, HK
    Biswas, G
    Robin, MA
    Avadhani, NG
    [J]. JOURNAL OF CELL BIOLOGY, 2003, 161 (01) : 41 - 54
  • [4] Transfer of beta-amyloid precursor protein gene using adenovirus vector causes mitochondrial abnormalities in cultured normal human muscle
    Askanas, V
    McFerrin, J
    Baque, S
    Alvarez, RB
    Sarkozi, E
    Engel, WK
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (03) : 1314 - 1319
  • [5] Experimental therapeutics in transgenic mouse models of Huntington's disease
    Beal, MF
    Ferrante, RJ
    [J]. NATURE REVIEWS NEUROSCIENCE, 2004, 5 (05) : 373 - 384
  • [6] Mitochondrial Dysfunction in Neurodegenerative Diseases
    Johri, Ashu
    Beal, M. Flint
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2012, 342 (03) : 619 - 630
  • [7] Amyloid β-protein toxicity and oxidative stress in Alzheimer's disease
    Behl, C
    [J]. CELL AND TISSUE RESEARCH, 1997, 290 (03) : 471 - 480
  • [8] Time sequence of maturation of dystrophic neurites associated with Aβ deposits in APP/PS1 transgenic mice
    Blanchard, V
    Moussaoui, S
    Czech, C
    Touchet, N
    Bonici, B
    Planche, M
    Canton, T
    Jedidi, I
    Gohin, M
    Wirths, O
    Bayer, TA
    Langui, D
    Duyckaerts, C
    Tremp, G
    Pradier, L
    [J]. EXPERIMENTAL NEUROLOGY, 2003, 184 (01) : 247 - 263
  • [9] BLASS JP, 1991, REV NEUROL, V147, P513
  • [10] Brain metabolism and brain disease: Is metabolic deficiency the proximate cause of Alzheimer dementia?
    Blass, JP
    [J]. JOURNAL OF NEUROSCIENCE RESEARCH, 2001, 66 (05) : 851 - 856