Department of Biochemistry, National Organization for Drug Control and Research (NODCAR), Egyptian Drug Authority (EDA), Cairo, Egypt.
Inflammopharmacology. 2023 Oct;31(5):2303-2310. doi: 10.1007/s10787-023-01270-5. Epub 2023 Jul 5.
Alzheimer's disease (AD) is a progressive type of neurodegenerative disease characterized by successive loss of the conventional structure and functions of neurons. In addition to dead neurons type detected within AD brain tissues, there are a predominantly varying number of deteriorating neurons (DTNs). As the number of deteriorating neurons increases, they exaggerate the release of inflammatory factors and oxidative stress that trigger the cascade of neuroinflammation. Triggering receptor expressed on myeloid cells 1 (TREM-1) which is a transmembrane immune receptor type regularly expressed by phagocytic cells, may act as a stimulating factor for neuroinflammation. Once TREM-1 is activated, it directly activates spleen tyrosine kinase (SYK) downstream signaling cascades, which can be considered an initiating phase for AD pathology and AD progression. Sequentially, SYK activates the pro-inflammatory microglia M1 phenotype which executes several inflammatory actions, leading to neurotoxicity. These released neurotoxins promote neuronal cell death, synaptic dysfunctions, and memory impairments. Thus, the current review outlines the direct etiological and pathologic features of Alzheimer's disease linked with deteriorating neurons, TREM-1, and SYK.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是神经元的常规结构和功能相继丧失。除了在 AD 脑组织中检测到的死亡神经元类型外，还有大量数量不断减少的神经元（DTNs）。随着减少神经元数量的增加，它们会加剧炎症因子和氧化应激的释放，从而引发神经炎症级联反应。触发表达在髓样细胞上的受体 1（TREM-1）是一种经常在吞噬细胞中表达的跨膜免疫受体，可能是神经炎症的刺激因素。一旦 TREM-1 被激活，它会直接激活脾酪氨酸激酶（SYK）下游信号级联反应，这可以被认为是 AD 病理和 AD 进展的起始阶段。随后，SYK 激活促炎小胶质细胞 M1 表型，执行几种炎症作用，导致神经毒性。这些释放的神经毒素促进神经元细胞死亡、突触功能障碍和记忆损伤。因此，本综述概述了与减少神经元、TREM-1 和 SYK 相关的阿尔茨海默病的直接病因和病理特征。
