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Lentiviral vector–mediated overexpression of Klotho in the brain improves Alzheimer's disease–like pathology and cognitive deficits in mice
journal contribution
posted on 2019-06-01, 00:00 authored by Chen-Ye Zeng, Ting-Ting Yang, Hong-Jing Zhou, Yue Zhao, Xi Kuang, Wei DuanWei Duan, Jun-Rong DuAlzheimer's disease (AD) is the most common type of senile dementia. The antiaging gene Klotho is reported to decline in the brain of patients and animals with AD. However, the role of Klotho in the progression of AD remains elusive. The present study explored the effects and underlying mechanism of Klotho in a mouse model of AD. The upregulation of cerebral Klotho expression was mediated by an intracerebroventricular injection of a lentiviral vector that encoded Klotho (LV-KL) in 7-month-old amyloid precursor protein/presenilin 1 transgenic mice. Three months later, LV-KL significantly induced Klotho overexpression in the brain and effectively ameliorated cognitive deficit and AD-like pathology in amyloid precursor protein/presenilin 1 mice. LV-KL induced autophagy activation and protein kinase B/mammalian target of rapamycin inhibition both in AD mice and BV2 murine microglia. These results suggest that the upregulation of Klotho expression in the brain may promote the autophagic clearance of amyloid beta and protect against cognitive deficits in AD mice. These findings highlight the preventive and therapeutic potential of Klotho for the treatment of AD.
History
Journal
Neurobiology of agingVolume
78Pagination
18 - 28Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
eISSN
1558-1497Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2019, Elsevier Inc.Usage metrics
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