A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer’s Disease

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dc.creatorKshirsagar, Sudhir
dc.creatorAlvir, Rainier Vladlen
dc.creatorPradeepkiran, Jangampalli Adi
dc.creatorHindle, Ashly
dc.creatorVijayan, Murali
dc.creatorRamasubramaniam, Bhagavathi
dc.creatorKumar, Subodh
dc.creatorReddy, Arubala P. (TTU)
dc.creatorReddy, P. Hemachandra (TTU)
dc.date.accessioned2023-03-28T20:16:44Z
dc.date.available2023-03-28T20:16:44Z
dc.date.issued2022
dc.description© 2022 by the authors. cc-by
dc.description.abstractIn the current study, for the first time, we study mitophagy enhancer urolithin A and a combination of urolithin A+green tea extract EGCG against human Aβ peptide-induced mitochondrial and synaptic, dendritic, inflammatory toxicities and behavioral changes in humanized homozygous amyloid beta knockin (hAbKI) mice of late-onset Alzheimer’s disease (AD). Our findings reveal significantly increased positive effects of urolithin A and a combination treatment of urolithin A+EGCG in hAbKI mice for phenotypic behavioral changes including motor coordination, locomotion/exploratory activity, spatial learning and working memory. mRNA and protein levels of mitochondrial fusion, synaptic, mitophagy and autophagy genes were upregulated, and mitochondrial fission genes are downregulated in urolithin A and combine treatment in hAbKI mice; however, the effect is stronger in combined treatment. Immunofluorescence analysis of hippocampal brain sections shows similar findings of mRNA and protein levels. Mitochondrial dysfunction is significantly reduced in both treatment groups, but a stronger reduction is observed in combined treatment. Dendritic spines and lengths are significantly increased in both treatment groups, but the effect is stronger in combined treatment. The fragmented number of mitochondria is reduced, and mitochondrial length is increased, and mitophagosomal formations are increased in both the groups, but the effect is stronger in the combined treatment. The levels of amyloid beta (Aβ) 40 and Aβ42 are reduced in both treatments, however, the reduction is higher for combined treatment. These observations suggest that urolithin A is protective against human Aβ peptide-induced toxicities; however, combined treatment of urolithin A+EGCG is effective and stronger, indicating that combined therapy is promising to treat late-onset AD patients.
dc.identifier.citationKshirsagar, S., Alvir, R.V., Pradeepkiran, J.A., Hindle, A., Vijayan, M., Ramasubramaniam, B., Kumar, S., Reddy, A.P., & Reddy, P.H.. 2022. A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer’s Disease. Cells, 11(17). https://doi.org/10.3390/cells11172660
dc.identifier.urihttps://doi.org/10.3390/cells11172660
dc.identifier.urihttps://hdl.handle.net/2346/92024
dc.language.isoeng
dc.subjectAlzheimer’s disease
dc.subjectamyloid beta
dc.subjectgreen tea extract EGCG
dc.subjecthumanized amyloid beta knockin mice
dc.subjectmitochondria
dc.subjecturolithin A
dc.titleA Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer’s Disease
dc.typeArticle

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