Hayden Melvin R, Tyagi Neetu
Department of Internal Medicine, Endocrinology Diabetes and Metabolism, Diabetes and Cardiovascular Disease Center, University of Missouri School of Medicine, One Hospital Drive, Columbia, MO 65211, USA.
Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Pharmaceuticals (Basel). 2024 Dec 23;17(12):1741. doi: 10.3390/ph17121741.
Late-onset Alzheimer's disease (LOAD) is a chronic, multifactorial, and progressive neurodegenerative disease that associates with aging and is highly prevalent in our older population (≥65 years of age). This hypothesis generating this narrative review will examine the important role for the use of sodium thiosulfate (STS) as a possible multi-targeting treatment option for LOAD. Sulfur is widely available in our environment and is responsible for forming organosulfur compounds that are known to be associated with a wide range of biological activities in the brain. STS is known to have (i) antioxidant and (ii) anti-inflammatory properties; (iii) chelation properties for calcium and the pro-oxidative cation metals such as iron and copper; (iv) donor properties for hydrogen sulfide production; (v) possible restorative properties for brain endothelial-cell-derived bioavailable nitric oxide. Thus, it becomes apparent that STS has the potential for neuroprotection and neuromodulation and may allow for an attenuation of the progressive nature of neurodegeneration and impaired cognition in LOAD. STS has been successfully used to prevent cisplatin oxidative-stress-induced ototoxicity in the treatment of head and neck and solid cancers, cyanide and arsenic poisoning, and fungal skin diseases. Most recently, intravenous STS has become part of the treatment plan for calciphylaxis globally due to vascular calcification and ischemia-induced skin necrosis and ulceration. Side effects have been minimal with reports of metabolic acidosis and increased anion gap; as with any drug treatment, there is also the possibility of allergic reactions, possible long-term osteoporosis from animal studies to date, and minor side-effects of nausea, headache, and rhinorrhea if infused too rapidly. While STS poorly penetrates the intact blood-brain barrier(s) (BBBs), it could readily penetrate BBBs that are dysfunctional and disrupted to deliver its neuroprotective and neuromodulating effects in addition to its ability to penetrate the blood-cerebrospinal fluid barrier of the choroid plexus. Novel strategies such as the future use of nano-technology may be helpful in allowing an increased entry of STS into the brain.
晚发性阿尔茨海默病（LOAD）是一种慢性、多因素且进行性的神经退行性疾病，与衰老相关，在老年人群（≥65岁）中高度流行。本综述所基于的假设将探讨硫代硫酸钠（STS）作为LOAD可能的多靶点治疗选择的重要作用。硫在我们的环境中广泛存在，负责形成有机硫化合物，已知这些化合物与大脑中的多种生物活性相关。已知STS具有（i）抗氧化和（ii）抗炎特性；（iii）对钙以及铁和铜等促氧化阳离子金属的螯合特性；（iv）产生硫化氢的供体特性；（v）对脑内皮细胞衍生的生物可利用一氧化氮的可能恢复特性。因此，很明显STS具有神经保护和神经调节的潜力，可能会减轻LOAD中神经退行性变和认知障碍的进行性发展。STS已成功用于预防顺铂氧化应激诱导的耳毒性，用于治疗头颈癌和实体癌、氰化物和砷中毒以及真菌性皮肤病。最近，由于血管钙化以及缺血诱导的皮肤坏死和溃疡，静脉注射STS已成为全球钙化防御治疗方案的一部分。副作用极小，有代谢性酸中毒和阴离子间隙增加的报告；与任何药物治疗一样，也有可能发生过敏反应，根据迄今为止的动物研究可能会出现长期骨质疏松，如果输注过快还会有恶心、头痛和鼻漏等轻微副作用。虽然STS很难穿透完整的血脑屏障（BBB），但它可以很容易地穿透功能失调和被破坏的BBB，以发挥其神经保护和神经调节作用，此外它还能够穿透脉络丛的血脑脊液屏障。诸如未来使用纳米技术等新策略可能有助于增加STS进入大脑的量。
