CNS SIRT3 Expression Is Altered by Reactive Oxygen Species and in Alzheimer’s Disease

PLoS One

Seth Love¹  Patrick G. Kehoe¹  Eric M. Verdin²  Tracey K. Murray³  Michael J. O’Neill³  Heather J. M. Weir⁴  Jon D. Lane⁴  Nina Balthasar⁵ 

[1] Dementia Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, United Kingdom;Gladstone Institute of Virology and Immunology, University of California San Francisco, San Francisco, California, United States of America;Neurodegenerative Diseases Drug Hunting Team, Eli Lilly and Co. Ltd., Windlesham, Surrey, United Kingdom;School of Biochemistry, University of Bristol, Bristol, United Kingdom;School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom

关键词: Mitochondria;    Alzheimer's disease;    Mouse models;    Central nervous system;    Neurons;    Oxidative stress;    Hippocampus;    Fluorescence imaging;   

DOI  :  10.1371/journal.pone.0048225

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Progressive mitochondrial dysfunction contributes to neuronal degeneration in age-mediated disease. An essential regulator of mitochondrial function is the deacetylase, sirtuin 3 (SIRT3). Here we investigate a role for CNS Sirt3 in mitochondrial responses to reactive oxygen species (ROS)- and Alzheimer’s disease (AD)-mediated stress. Pharmacological augmentation of mitochondrial ROS increases Sirt3 expression in primary hippocampal culture with SIRT3 over-expression being neuroprotective. Furthermore, Sirt3 expression mirrors spatiotemporal deposition of β-amyloid in an AD mouse model and is also upregulated in AD patient temporal neocortex. Thus, our data suggest a role for SIRT3 in mechanisms sensing and tackling ROS- and AD-mediated mitochondrial stress.

【 授权许可】

CC BY