Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
Oklahoma City VA Medical Center, Oklahoma City, OK, USA.
Skelet Muscle. 2021 Nov 12;11(1):25. doi: 10.1186/s13395-021-00280-7.
As a key regulator of cellular calcium homeostasis, the Sarcoendoplasmic Reticulum Calcium ATPase (SERCA) pump acts to transport calcium ions from the cytosol back to the sarcoplasmic reticulum (SR) following muscle contraction. SERCA function is closely associated with muscle health and function, and SERCA activity is susceptible to muscle pathogenesis. For example, it has been well reported that pathological conditions associated with aging, neurodegeneration, and muscular dystrophy (MD) significantly depress SERCA function with the potential to impair intracellular calcium homeostasis and further contribute to muscle atrophy and weakness. As a result, targeting SERCA activity has attracted attention as a therapeutical method for the treatment of muscle pathologies. The interventions include activation of SERCA activity and genetic overexpression of SERCA. This review will focus on SERCA function and regulation mechanisms and describe how those mechanisms are affected under muscle pathological conditions including elevated oxidative stress induced by aging, muscle disease, or neuromuscular disorders. We also discuss the current progress and therapeutic approaches to targeting SERCA in vivo.
作为细胞钙稳态的关键调节剂，肌浆网内质网钙 ATP 酶（SERCA）泵在肌肉收缩后将钙离子从细胞质中运回到肌浆网（SR）。SERCA 的功能与肌肉健康和功能密切相关，并且 SERCA 的活性易受肌肉发病机制的影响。例如，已有充分的报道表明，与衰老、神经退行性变和肌营养不良症（MD）相关的病理状况会显著降低 SERCA 的功能，从而有可能损害细胞内钙稳态，并进一步导致肌肉萎缩和无力。因此，靶向 SERCA 活性已作为治疗肌肉病理的治疗方法引起了关注。这些干预措施包括激活 SERCA 活性和 SERCA 的基因过表达。本综述将重点介绍 SERCA 的功能和调节机制，并描述在肌肉病理条件下这些机制是如何受到影响的，包括由衰老、肌肉疾病或神经肌肉疾病引起的氧化应激升高。我们还讨论了靶向 SERCA 在体内的当前进展和治疗方法。
