PDF(Pubmed)
Abstract：
Although apoptosis, pyroptosis, and ferroptosis have been implicated in AD, none fully explains the extensive neuronal loss observed in AD brains. Recent evidence shows that necroptosis is abundant in AD, that necroptosis is closely linked to the appearance of Tau pathology, and that necroptosis markers accumulate in granulovacuolar neurodegeneration vesicles (GVD). We review here the neuron-specific activation of the granulovacuolar mediated neuronal-necroptosis pathway, the potential AD-relevant triggers upstream of this pathway, and the interaction of the necrosome with the endo-lysosomal pathway, possibly providing links to Tau pathology. In addition, we underscore the therapeutic potential of inhibiting necroptosis in neurodegenerative diseases such as AD, as this presents a novel avenue for drug development targeting neuronal loss to preserve cognitive abilities. Such an approach seems particularly relevant when combined with amyloid-lowering drugs.
摘要：
虽然凋亡，焦亡,铁性凋亡与AD有关，没有完全解释在AD脑中观察到的广泛的神经元丢失。最近的证据表明，坏死性凋亡在AD中很丰富，坏死与Tau病理学的出现密切相关，并且坏死标记物积聚在颗粒液泡神经变性囊泡（GVD）中。我们在这里回顾了颗粒液泡介导的神经元坏死途径的神经元特异性激活，该通路上游的潜在AD相关触发因素，以及坏死体与内溶酶体途径的相互作用，可能提供与Tau病理学的联系.此外,我们强调了抑制神经退行性疾病如AD的坏死的治疗潜力，因为这为针对神经元丢失以保持认知能力的药物开发提供了新的途径。当与降低淀粉样蛋白的药物组合时,这种方法似乎特别相关。
