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Exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway. | LitMetric

Exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway.

CNS Neurosci Ther

Department of Pharmacology, Laboratory of Aging and Nervous Diseases (SZS0703), Soochow University School of Pharmaceutical Science, Su Zhou, China.

Published: June 2019

AI Article Synopsis

  • - The study investigated how exercise influences lysosomal functions, using mice that ran on wheels for 8 weeks while some were given an SIRT1 inhibitor to observe effects on lysosomal activity.
  • - Results indicated that exercise enhances the movement of TFEB protein into the nucleus, which increases the production of genes related to autophagy and lysosomal function through the AMPK-SIRT1 signaling pathway.
  • - Long-term exercise was found to have a greater impact on lysosomal biogenesis compared to short-term exercise, suggesting significant benefits for brain health through regular running activity.

Article Abstract

Aim: To study the effects of exercise on lysosomal functions.

Methods: Mouse exercise model was established and wheel running was scheduled as 18 rpm (14:00-17:00), 5 d/wk, for 8 weeks. Mice were injected EX527 to inhibit SIRT1 activity. The protein level was assayed with Western blot and immunofluorescence histochemistry. The transmission electron microscopic examination was used to show the structure of lysosome and mitochondria.

Results: Exercise promoted the nuclear translocation of TFEB in the cortex which upregulated the transcription of genes associated with autophagy and lysosome. Exercise directly activated autophagy/lysosome system via up-regulating of AMPK-SIRT1 signaling. The SIRT1 inhibitor EX527 decreased TFEB regulated gene transcription but had little effect on the nuclear translocation of TFEB. In addition, long-term exercise showed more significant effects on activation of lysosomes biogenesis compared with the short-term exercise and trehalose, a classical autophagy activator in the mTOR-independent pathway.

Conclusion: Running exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515701PMC
http://dx.doi.org/10.1111/cns.13114DOI Listing

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