| First Author | Lee HJ | Year | 2023 |
| Journal | Mol Brain | Volume | 16 |
| Issue | 1 | Pages | 63 |
| PubMed ID | 37580778 | Mgi Jnum | J:339358 |
| Mgi Id | MGI:7519809 | Doi | 10.1186/s13041-023-01051-9 |
| Citation | Lee HJ, et al. (2023) Profiling tyrosine kinase inhibitors as AD therapeutics in a mouse model of AD. Mol Brain 16(1):63 |
| abstractText | Alzheimer's disease (AD) is a neurodegenerative disease characterized by Abeta deposition, tauopathy, neuroinflammation, and impaired cognition. The recent identification of associations between protein kinases and AD pathology has spurred interest in tyrosine kinase inhibitors (TKIs) as potential strategic therapeutic agents for AD. In the present study, we investigated whether the TKIs ibrutinib, PD180970, and cabozantinib, which have different on-targets, selectively regulate AD pathology in 3.5- to 4-month-old 5xFAD mice (a model of the early phase of AD). Ibrutinib (10 mg/kg, i.p.) effectively reduced amyloid-beta (Abeta) plaque number, tau hyperphosphorylation and neuroinflammation in 5xFAD mice. Surprisingly, PD180970 (10 mg/kg, i.p.) did not alter Abeta plaque number or neuroinflammatory responses and exacerbated tau hyperphosphorylation in 5xFAD mice. Cabozantinib (10 mg/kg, i.p.) had no effect on amyloidopathy but partially relieved tau hyperphosphorylation and astrogliosis. Taken together, our results suggest that not all TKIs have therapeutic effects on AD pathology in a mouse model of AD. Consequently, optimization of drug dosage, injection periods and administration routes should be considered when repurposing TKIs as novel AD therapeutics. |
