Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease

作者：Underwood Benjamin R; Imarisio Sara; Fleming Angeleen; Rose Claudia; Krishna Gauri; Heard Phoebe; Quick Marie; Korolchuk Viktor I; Renna Maurizio; Sarkar Sovan; Garcia Arencibia Moises; O'Kane Cahir J; Murphy Michael P; Rubinsztein David C^*

来源：Human Molecular Genetics, 2010, 19(17): 3413-3429.

DOI：10.1093/hmg/ddq253

Many neurodegenerative diseases exhibit protein accumulation and increased oxidative stress. Therapeutic strategies include clearing aggregate-prone proteins by enhancing autophagy or decreasing oxidative stress with antioxidants. Many autophagy-inducing stimuli increase reactive oxygen species (ROS), raising concerns that the benefits of autophagy up-regulation may be counterbalanced by ROS toxicity. Here we show that not all autophagy inducers significantly increase ROS. However, many antioxidants inhibit both basal and induced autophagy. By blocking autophagy, antioxidant drugs can increase the levels of aggregate-prone proteins associated with neurodegenerative disease. In fly and zebrafish models of Huntington's disease, antioxidants exacerbate the disease phenotype and abrogate the rescue seen with autophagy-inducing agents. Thus, the potential benefits in neurodegenerative diseases of some classes of antioxidants may be compromised by their autophagy-blocking properties.

• 出版日期2010-9-1
• 单位河北医科大学