Elendu Chukwuka, Amaechi Dependable C, Elendu Tochi C, Amaechi Emmanuel C, Elendu Ijeoma D, Ajakaye Abolore Aminat, Ubi Esther S, Ikejig Victor I, Okwunweze Kosisochukwu T, Debua Ayi T, Eze John A, Ugwu Emmanuel J
Federal University Teaching Hospital, Owerri, Nigeria.
Igbinedion University, Okada, Nigeria.
Ann Med Surg (Lond). 2025 May 30;87(7):4281-4302. doi: 10.1097/MS9.0000000000003438. eCollection 2025 Jul.
The discovery and subsequent evolution of the Ouabain-Na/K pump endocrine system have profoundly impacted our understanding of cellular physiology and disease mechanisms. Initially identified as a cardiotonic steroid with potent effects on the Na/K ATPase, Ouabain has been implicated in various physiological and pathological processes. The Na/K pump, a crucial component of cellular physiology, maintains electrochemical gradients essential for nerve impulse transmission, muscle contraction, and cellular volume regulation. Since Jens Christian Skou's Nobel Prize-winning discovery in 1957, research has unveiled its broader role in cellular homeostasis and disease. A significant breakthrough was the identification of Ouabain as an endogenous ligand of the Na/K pump, transforming the pump's role from a mere ion transporter to a receptor within a hormonal signaling pathway. This discovery has linked the Na/K pump to complex intracellular signaling pathways, with implications for hypertension, heart failure, and cancer. However, emerging evidence suggests that its role extends beyond cardiovascular dysfunction to neurological disorders such as epilepsy, Alzheimer's disease, and Parkinson's disease. In epilepsy, dysregulation of the Na/K pump contributes to altered ion homeostasis and hyperexcitability. At the same time, in Alzheimer's disease, its dysfunction has been associated with disrupted calcium signaling, oxidative stress, and amyloid-beta accumulation. Similarly, alterations in Na/K pump activity have been linked to dopaminergic neuron vulnerability in Parkinson's disease. This paradigm shift offers exciting therapeutic possibilities for neurodegenerative and neuropsychiatric disorders, including schizophrenia and depression, redefining the pump's significance across multiple disciplines of medicine.
哇巴因 - 钠钾泵内分泌系统的发现及其后续演变对我们理解细胞生理学和疾病机制产生了深远影响。哇巴因最初被鉴定为一种对钠钾ATP酶有强效作用的强心甾体，已被证明与各种生理和病理过程有关。钠钾泵是细胞生理学的关键组成部分，维持着神经冲动传递、肌肉收缩和细胞体积调节所必需的电化学梯度。自1957年延斯·克里斯蒂安·斯科获得诺贝尔奖的发现以来，研究揭示了其在细胞稳态和疾病中的更广泛作用。一个重大突破是确定哇巴因是钠钾泵的内源性配体，这将泵的作用从单纯的离子转运体转变为激素信号通路中的受体。这一发现将钠钾泵与复杂的细胞内信号通路联系起来，对高血压、心力衰竭和癌症具有重要意义。然而，新出现的证据表明，其作用不仅限于心血管功能障碍，还涉及癫痫、阿尔茨海默病和帕金森病等神经系统疾病。在癫痫中，钠钾泵的失调导致离子稳态改变和兴奋性增加。同时，在阿尔茨海默病中，其功能障碍与钙信号紊乱、氧化应激和β淀粉样蛋白积累有关。同样，钠钾泵活性的改变与帕金森病中多巴胺能神经元的易损性有关。这种范式转变为神经退行性和神经精神疾病（包括精神分裂症和抑郁症）提供了令人兴奋的治疗可能性，重新定义了该泵在多个医学学科中的重要性。
