1. Academic Validation
  2. Inhibition of caspase-1 ameliorates tauopathy and rescues cognitive impairment in SAMP8 mice

Inhibition of caspase-1 ameliorates tauopathy and rescues cognitive impairment in SAMP8 mice

  • Metab Brain Dis. 2022 Apr;37(4):1197-1205. doi: 10.1007/s11011-022-00914-9.
Meng-Shan Tan 1 Yi Liu 2 Hao Hu 2 Chen-Chen Tan 2 Lan Tan 3
Affiliations

Affiliations

  • 1 Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, People's Republic of China. tanmengshan@163.com.
  • 2 Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, People's Republic of China.
  • 3 Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, People's Republic of China. dr.tanlan@163.com.
Abstract

The inflammasome assembles leading to increased cleavage and activity of Caspase-1 and downstream IL-1β release, which plays a significant role in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that caspase-1-mediated neuroinflammation occurs early in AD process. However, the detailed role of Caspase-1 in aging-related AD-like neuropathology is still unclear so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we detected the levels of Caspase-1 in brains of 3-, 7-, and 11-month-old mice and observed that Caspase-1 was activated during aging process. More importantly, we provided the evidence that VX-765, a selective inhibitor of Caspase-1, significantly rescued spatial learning and memory impairments and reduced tau hyperphosphorylation in brains of SAMP8 mice at early stages of the disease. This amelioration might be attributed to IL-1β-induced hypoactivation of tau kinases. Our results imply that Caspase-1 may represent as a potential therapeutic target for neurodegenerative tauopathies.

Keywords

Caspase-1; SAMP8; Spatial cognitive deficits; Tau hyperphosphorylation; VX-765.

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