Regulation of autophagy by Na+/H+exchangers

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Autophagy is an intracellular degradation process that clears long-lived proteins and organelles from the cytoplasm, and then maintains normal cellular functions. Thus failure of autophagy in neurons can result in the accumulation of aggregate-prone proteins and neurodegeneration. However, the regulation mechanism of autophagy in brain is less known. In the present study, I found that an NHE blocker inhibited autophagy and that the over expression of plasma membrane type NHEs significantly reduced the formation of poly glutamine aggregation in a cell-line. Moreover, NHE5KO/Htt-Tg mice were generated by crossing with NHE5 knockout mouse and a Huntington's disease model mouse in which a large number of aggregations were observed in the cerebellar granule cells.