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

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Potassium-chelating drug sodium polystyrene sulfonate enhances lysosomal function and suppresses proteotoxicity
GeroScience ( IF 5.3 ) Pub Date : 2022-08-26 , DOI: 10.1007/s11357-022-00647-8
Cyrene Arputhasamy ₁ , Anna C Foulger ₁ , Mark Lucanic ₁ , Anand Rane ₁ , Minna Schmidt _{1,

2} , Theo Garrett ₁ , Michael Broussalian _{1,

3} , Elena Battistoni _{1,

3} , Rachel B Brem _{1,

4} , Gordon J Lithgow _{1,

2} , Manish Chamoli ₁ , Julie K Andersen _{1,

2}

Affiliation

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.

中文翻译：

钾螯合药物聚苯乙烯磺酸钠可增强溶酶体功能并抑制蛋白质毒性

摘要

溶酶体对于受损蛋白质和细胞成分的降解和循环至关重要。增强溶酶体功能的治疗策略是治疗衰老和与年龄相关的神经退行性疾病的一种很有前途的方法。在这里，我们展示了 FDA 批准的用于降低人体高血钾的药物聚苯乙烯磺酸钠 (SPS)，增强了秀丽隐杆线虫和人类神经元细胞中的溶酶体功能。SPS 处理后溶酶体功能的增强伴随着由神经毒性肽 Aβ 和 TAU 的表达引起的蛋白毒性的抑制。此外，使用 SPS 处理可显着延长秀丽隐杆线虫的寿命，从而带来健康益处. 总的来说，我们的工作支持将 SPS 作为一种前瞻性的老年保护干预措施的潜在用途。

更新日期：2022-08-27

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