To prevent neurodegeneration

Abstract

Neurodegenerative diseases are characterized by progressive dysfunction and death of neurons in specific areas of the nervous system. Loss of neurons is often associated with multiple stresses such as abnormal aggregation of misfolded proteins, deficiency of protein degradation system, mitochondrial dysfunction and excessive oxidative products. HDAC6 has recently been suggested to be an integral factor that copes with these stresses. In this mini-review, we summarize our current understanding of how HDAC6 promotes inclusion formation, facilitates autophagic degradation of protein aggregates and dysfunctional mitochondria. Finally, the possibility for HDAC6 to be a potential preventional and therapeutical target of some neurodegenerative diseases is put forward.

Acknowledgements

This work has been financially supported by the 973 program (2009CB918702), the NSFC (30623005, 31071087 and 30771217).

Figures and Tables

Figure 1 A model of how HDAC6 functions in different pathways to cope with different cellular stresses. Oligomers derived from self-assembly of aggregation-prone proteins are a major cause of several neurodegenerative diseases. An immediate strategy for HDAC6 to cope with the toxic oligomers is to bind to and promote them to form inclusions. The ultimate strategy for HDAC6 to eliminate these nonfunctional protein aggregates is to facilitate autophagic degradation of these aggregated inclusions. Another strategy for HDAC6, when the neurons are challenged by mitochondrial dysfunction, is to promote mitophagy. Mitochondrial dysfunction may lead to oxidative stress and cytochrome c release, which are toxic to the cells. IB, inclusion body; Cyt c, cytochrome c; OS, oxidative stress.