小胶质细胞谷氨酸受体的功能障碍可能导致神经退行性变化

Title:Dysfunction of Glutamate Receptors in Microglia May Cause Neurodegeneration

Volume: 13 Issue: 4

Author(s): Mami Noda

Affiliation:

关键词: AMPA受体；GluA2；钙离子的通透性；小胶质细胞；神经退行性疾病；肿瘤坏死因子-α

摘要: Dysregulation of glutamate signalling is important in Alzheimer's disease and other pathologies. There has been a focus on changes in neuronal glutamate signalling, but microglia also express glutamate receptors (GluRs), which are known to modulate their responses to neuropathology. Microglia express both metabotropic and ionotropic GluRs. Among ionotropic GluRs, microglial AMPA (α-amino-hydroxy-5-methyl-isoxazole-4-propionate)-type of GluRs (AMPA-Rs) are Ca²⁺ impermeable due to the expression of subunit GluA2. Upon activation of microglia, expression level of surface GluA2 subunits significantly increase, while expression of GluA1, A3 and A4 subunits on membrane surface significantly decrease. Owing to the GluA2 subunits-dominant composition, AMPA-Rs in activated microglia show little response to Glu. On the other hand, microglia lacking GluA2 show higher Ca²⁺-permeability, consequently inducing a significant increase in the release of the pro-inflammatory cytokine, such as TNF-α. It is suggested that membrane translocation of GluA2-containing AMPA-Rs in activated microglia has functional importance. Thus, dysfunction or decreased expression of GluA2 reported in patients with neurodegenerative diseases such as Alzheimer’s and Creutzfeldt-Jakob disease may accelerate Glu neurotoxicity via excess release of proinflammatory cytokines from microglia, causing more neuronal death.

Cite this article as:

Mami Noda , Dysfunction of Glutamate Receptors in Microglia May Cause Neurodegeneration, Current Alzheimer Research 2016; 13 (4) . https://dx.doi.org/10.2174/1567205013666151116125810