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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 (A\u03b2) 40 and A\u03b242 are reduced in both treatments, however, the reduction is higher for combined treatment. These observations suggest that urolithin A is protective against human A\u03b2 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.<\/jats:p>","DOI":"10.3390\/cells11172660","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T21:22:56Z","timestamp":1661721776000},"page":"2660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["RETRACTED: 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\u2019s Disease"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-7459","authenticated-orcid":false,"given":"Sudhir","family":"Kshirsagar","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainier","family":"Alvir","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4678-6443","authenticated-orcid":false,"given":"Jangampalli","family":"Pradeepkiran","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashly","family":"Hindle","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-3415","authenticated-orcid":false,"given":"Murali","family":"Vijayan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagavathi","family":"Ramasubramaniam","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4705-122X","authenticated-orcid":false,"given":"Subodh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA"},{"name":"Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0452-9553","authenticated-orcid":false,"given":"Arubala","family":"Reddy","sequence":"additional","affiliation":[{"name":"Nutritional Sciences Department, College of Human Sciences, Texas Tech University, 1301 Akron Ave, Lubbock, TX 79409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-9948","authenticated-orcid":false,"given":"P.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA"},{"name":"Nutritional Sciences Department, College of Human Sciences, Texas Tech University, 1301 Akron Ave, Lubbock, TX 79409, USA"},{"name":"Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Public Health, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Speech, Language, and Hearing Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1152\/physrev.2001.81.2.741","article-title":"Alzheimer\u2019s disease: Genes, proteins, and therapy","volume":"81","author":"Selkoe","year":"2001","journal-title":"Physiol. 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