Signum Biosciences, Princeton, NJ, 08540, USA.
Center for Public Health Initiatives, University of Pennsylvania, Philadelphia, PA, 9104, USA.
Neurochem Int. 2021 Feb;143:104936. doi: 10.1016/j.neuint.2020.104936. Epub 2020 Dec 10.
Long term consequence of non-fatal overdose in people who use opioids are not well understood. The intermittent exposure to non-fatal overdose leads to a tauopathy that is often accompanied by abrogated neuroprotective response, abnormal amyloid processing and other pathologies. The scope and limitations of available literature are discussed including neuropathologies associated with opioid and overdose exposures, contributing comorbidities and proteinopathies. Contrasting postmortem data of overdose victims with animal models of opioid neuropathologies and hypoxic injury paints a picture distinct from other proteinopathies as well as effects of moderate opioid exposure. Furthermore the reported biochemical changes and potential targets for therapeutic intervention were mapped pointing to underlying imbalance between tau kinases and phosphatases that is characteristic of Alzheimer Disease.
长期使用阿片类药物的非致命性过量的后果尚不清楚。间歇性暴露于非致命性过量会导致 tau 病，通常伴随着神经保护反应减弱、异常淀粉样蛋白处理和其他病理学改变。本文讨论了现有文献的范围和局限性，包括与阿片类药物和过量暴露相关的神经病理学、促成的合并症和蛋白病。过量死亡受害者的尸检数据与阿片类药物神经病理学和缺氧损伤的动物模型形成鲜明对比，与其他蛋白病以及中度阿片类药物暴露的影响也形成鲜明对比。此外，还绘制了报告的生化变化和潜在的治疗干预靶点，指向 tau 激酶和磷酸酶之间失衡的潜在机制，这是阿尔茨海默病的特征。
