阿尔茨海默病星形胶质细胞神经毒性的多样性和调控

Title:Diversity and Regulation of Astrocyte Neurotoxicity in Alzheimer's Disease

Volume: 18 Issue: 12

关键词: 反应性星形胶质细胞、神经变性、小胶质细胞、活性氧、活性氮、肿瘤坏死因子 α、谷氨酸、基质金属蛋白酶。

摘要: Astrocytes contribute to brain development and homeostasis and support diverse functions of neurons. These cells also respond to the pathological processes in Alzheimer’s disease (AD). There is still considerable debate concerning the overall contribution of astrocytes to AD pathogenesis since both the protective and harmful effects of these cells on neuronal survival have been documented. This review focuses exclusively on the neurotoxic potential of astrocytes while acknowledging that these cells can contribute to neurodegeneration through other mechanisms, for example, by lowered neurotrophic support. We identify reactive oxygen and nitrogen species, tumor necrosis factor α (TNF-α), glutamate, and matrix metalloproteinase (MMP)-9 as molecules that can be directly toxic to neurons and are released by reactive astrocytes. There is also considerable evidence suggesting their involvement in AD pathogenesis. We further discuss the signaling molecules that trigger the neurotoxic response of astrocytes with a focus on human cells. We also highlight microglia, the immune cells of the brain, as critical regulators of astrocyte neurotoxicity. Nuclear imaging and magnetic resonance spectroscopy (MRS) could be used to confirm the contribution of astrocyte neurotoxicity to AD progression. The molecular mechanisms discussed in this review could be targeted in the development of novel therapies for AD.

Cite this article as:

Diversity and Regulation of Astrocyte Neurotoxicity in Alzheimer's Disease, Current Alzheimer Research 2021; 18 (12) . https://dx.doi.org/10.2174/1567205018666211117100342