Clinic of Internal Medicine III, Division of Nephrology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
Medizinische Klinik und Poliklinik IV, Hospital of the Ludwig-Maximilian-University Munich, Munich, Germany.
Nat Rev Endocrinol. 2021 Aug;17(8):497-510. doi: 10.1038/s41574-021-00499-w. Epub 2021 Jun 16.
The death of endocrine cells is involved in type 1 diabetes mellitus, autoimmunity, adrenopause and hypogonadotropism. Insights from research on basic cell death have revealed that most pathophysiologically important cell death is necrotic in nature, whereas regular metabolism is maintained by apoptosis programmes. Necrosis is defined as cell death by plasma membrane rupture, which allows the release of damage-associated molecular patterns that trigger an immune response referred to as necroinflammation. Regulated necrosis comes in different forms, such as necroptosis, pyroptosis and ferroptosis. In this Perspective, with a focus on the endocrine environment, we introduce these cell death pathways and discuss the specific consequences of regulated necrosis. Given that clinical trials of necrostatins for the treatment of autoimmune conditions have already been initiated, we highlight the therapeutic potential of such novel therapeutic approaches that, in our opinion, should be tested in endocrine disorders in the future.
胰岛细胞死亡与 1 型糖尿病、自身免疫、肾上腺功能减退和促性腺激素分泌不足有关。基础细胞死亡研究的新发现表明，大多数与病理生理学相关的细胞死亡本质上是坏死，而凋亡程序则维持着常规的代谢。坏死被定义为细胞膜破裂导致的细胞死亡，这会导致损伤相关分子模式的释放，从而引发被称为坏死性炎症的免疫反应。受调控的细胞坏死有多种形式，如坏死性凋亡、细胞焦亡和铁死亡。在这篇观点文章中，我们重点关注内分泌环境，介绍这些细胞死亡途径，并讨论受调控的细胞坏死的具体后果。鉴于已经开始了针对自身免疫性疾病的坏死抑制剂的临床试验，我们强调了这些新型治疗方法的治疗潜力，我们认为，这些方法在未来应该在内分泌疾病中进行测试。
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