| First Author | Lu Y | Year | 2023 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1869 |
| Issue | 8 | Pages | 166841 |
| PubMed ID | 37558011 | Mgi Jnum | J:339359 |
| Mgi Id | MGI:7519886 | Doi | 10.1016/j.bbadis.2023.166841 |
| Citation | Lu Y, et al. (2023) Bezafibrate confers neuroprotection in the 5xFAD mouse model of Alzheimer's disease. Biochim Biophys Acta Mol Basis Dis 1869(8):166841 |
| abstractText | Mitochondrial dysfunction plays an important role in the pathogenesis of Alzheimer's disease (AD), the most common neurodegenerative disease. Prior studies suggested impaired mitochondrial biogenesis likely contributes to mitochondrial dysfunction in AD. Bezafibrate, a peroxisome proliferator-activated receptor (PPAR) pan-agonist, has been shown to enhance mitochondrial biogenesis and increase oxidative phosphorylation capacity. In the present study, we investigated whether bezafibrate could rescue mitochondrial dysfunction and other AD-related deficits in 5xFAD mice. Bezafibrate was well tolerated by 5xFAD mice. Indeed, it rescued the expression of key mitochondrial proteins as well as mitochondrial dynamics and function in the brain of 5xFAD mice. Importantly, bezafibrate treatment led to significant improvement of cognitive/memory function in 5xFAD mice accompanied by alleviation of amyloid pathology and neuronal loss as well as reduced oxidative stress and neuroinflammation. Overall, this study suggests that bezafibrate improves mitochondrial function, mitigates neuroinflammation and improves cognitive functions in 5xFAD mice, thus supporting the notion that enhancing mitochondrial biogenesis/function is a promising therapeutic strategy for AD. |
