Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: Implications to mitochondria-targeted antioxidant therapeutics

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Review

Reddy, P. Hemachandra^1,2  Tripathi, Raghav¹  Quang Troung¹  Tirumala, Karuna¹  Reddy, Tejaswini P.¹  Anekonda, Vishwanath¹  Shirendeb, Ulziibat P.¹  Calkins, Marcus J.¹  Reddy, Arubala P.¹  Mao, Peizhong¹  Manczak, Maria¹ 

[1] Oregon Hlth & Sci Univ, Neurogenet Lab, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA

[2] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA

关键词: Alzheimer's disease;    Antioxidant;    Primary neuron;    Reactive oxygen species;    Amyloid beta;    Amyloid precursor protein;   

DOI  :  10.1016/j.bbadis.2011.10.011

来源: Elsevier

【 摘 要 】

Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer's disease (AD) progression. Loss of synapses and synaptic damage are the best correlates of cognitive deficits found in AD patients. Recent research on amyloid beta (A beta) and mitochondria in AD revealed that A beta accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (A beta PP) transgenic mice revealed reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that A beta, is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in A beta-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

Free