嘌呤核苷磷酸化酶作为治疗与年龄相关的下尿路功能障碍的靶点。
Purine nucleoside phosphorylase as a target to treat age-associated lower urinary tract dysfunction.
机构信息
Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
出版信息
Nat Rev Urol. 2022 Nov;19(11):681-687. doi: 10.1038/s41585-022-00642-w. Epub 2022 Sep 7.
The lower urinary tract (LUT), including the bladder, urethra and external striated muscle, becomes dysfunctional with age; consequently, many older individuals suffer from lower urinary tract disorders (LUTDs). By compromising urine storage and voiding, LUTDs degrade quality of life for millions of individuals worldwide. Treatments for LUTDs have been disappointing, frustrating both patients and their physicians; however, emerging evidence suggests that partial inhibition of the enzyme purine nucleoside phosphorylase (PNPase) with 8-aminoguanine (an endogenous PNPase inhibitor that moderately reduces PNPase activity) reverses age-associated defects in the LUT and restores the LUT to that of a younger state. Thus, 8-aminoguanine improves LUT biochemistry, structure and function by rebalancing the LUT purine metabolome, making 8-aminoguanine a novel potential treatment for LUTDs.
下尿路（LUT）包括膀胱、尿道和外部横纹肌，随年龄增长而出现功能障碍；因此，许多老年人患有下尿路疾病（LUTD）。LUTD 通过损害尿液储存和排空，降低了全球数百万人的生活质量。LUTD 的治疗一直令人失望，令患者及其医生都感到沮丧；然而，新出现的证据表明，用 8-氨基鸟嘌呤（一种内源性 PNPase 抑制剂，可适度降低 PNPase 活性）部分抑制嘌呤核苷磷酸化酶（PNPase）可逆转 LUT 与年龄相关的缺陷，并使 LUT 恢复到年轻状态。因此，8-氨基鸟嘌呤通过重新平衡 LUT 嘌呤代谢组来改善 LUT 的生物化学、结构和功能，使 8-氨基鸟嘌呤成为 LUTD 的一种新的潜在治疗方法。
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