Departments of Biology, Neurobiology, and Bio-X, Stanford University, Stanford, CA 94305, U.S.A.
Biosci Rep. 2024 Feb 29;44(2). doi: 10.1042/BSR20222267.
Aging brings about a myriad of degenerative processes throughout the body. A decrease in cognitive abilities is one of the hallmark phenotypes of aging, underpinned by neuroinflammation and neurodegeneration occurring in the brain. This review focuses on the role of different immune receptors expressed in cells of the central and peripheral nervous systems. We will discuss how immune receptors in the brain act as sentinels and effectors of the age-dependent shift in ligand composition. Within this 'old-age-ligand soup,' some immune receptors contribute directly to excessive synaptic weakening from within the neuronal compartment, while others amplify the damaging inflammatory environment in the brain. Ultimately, chronic inflammation sets up a positive feedback loop that increases the impact of immune ligand-receptor interactions in the brain, leading to permanent synaptic and neuronal loss.
衰老是全身多种退行性过程的结果。认知能力下降是衰老的标志性表型之一,其基础是大脑中的神经炎症和神经退行性变。本综述重点讨论了中枢和外周神经系统细胞中表达的不同免疫受体的作用。我们将讨论大脑中的免疫受体如何作为年龄相关配体组成变化的哨兵和效应物。在这种“老年配体汤”中,一些免疫受体直接导致神经元内部过度的突触减弱,而另一些则放大大脑中破坏性的炎症环境。最终,慢性炎症形成了一个正反馈循环,增加了大脑中免疫配体-受体相互作用的影响,导致永久性的突触和神经元丧失。