Potassium-chelating drug sodium polystyrene sulfonate enhances lysosomal function and suppresses proteotoxicity

钾螯合药物聚苯乙烯磺酸钠增强溶酶体功能并抑制蛋白质毒性

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作者:Cyrene Arputhasamy #, Anna C Foulger #, Mark Lucanic, Anand Rane, Minna Schmidt, Theo Garrett, Michael Broussalian, Elena Battistoni, Rachel B Brem, Gordon J Lithgow, Manish Chamoli, Julie K Andersen

Abstract

Lysosomes are crucial for degradation and recycling of damaged proteins and cellular components. Therapeutic strategies enhancing lysosomal function are a promising approach for aging and age-related neurodegenerative diseases. Here, we show that an FDA approved drug sodium polystyrene sulfonate (SPS), used to reduce high blood potassium in humans, enhances lysosomal function both in C. elegans and in human neuronal cells. Enhanced lysosomal function following SPS treatment is accompanied by the suppression of proteotoxicity caused by expression of the neurotoxic peptides Aβ and TAU. Additionally, treatment with SPS imparts health benefits as it significantly increases lifespan in C. elegans. Overall our work supports the potential use of SPS as a prospective geroprotective intervention.

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