| First Author | Hu J | Year | 2023 |
| Journal | Neuron | Volume | 111 |
| Issue | 1 | Pages | 15-29.e8 |
| PubMed ID | 36368316 | Mgi Jnum | J:332626 |
| Mgi Id | MGI:7424740 | Doi | 10.1016/j.neuron.2022.10.021 |
| Citation | Hu J, et al. (2023) Microglial Piezo1 senses Abeta fibril stiffness to restrict Alzheimer's disease. Neuron 111(1):15-29.e8 |
| abstractText | The pathology of Alzheimer's disease (AD) is featured with extracellular amyloid-beta (Abeta) plaques, whose impact on the mechanical properties of the surrounding brain tissues is unclear. Microglia sense and integrate biochemical cues of the microenvironment. However, whether the microglial mechanosensing pathways influence AD pathogenesis is unknown. Here, we surveyed the elevated stiffness of Abeta-plaque-associated tissues and observed the selective upregulation of the mechanosensitive ion channel Piezo1 in Abeta-plaque-associated microglia. Piezo1 sensed the stiffness stimuli of Abeta fibrils and subsequently induced Ca(2+) influx for microglial clustering, phagocytosis, and compacting of Abeta plaques. Microglia lacking Piezo1 led to the exacerbation of Abeta pathology and cognitive decline, whereas pharmacological activation of microglial Piezo1 ameliorated brain Abeta burden and cognitive impairment in 5 x FAD mice. Together, our results reveal that Piezo1, a mechanosensor of Abeta fibril stiffness in microglia, represents a potential therapeutic target for AD. |
