{"id":4976,"date":"2015-04-10T10:18:58","date_gmt":"2015-04-10T10:18:58","guid":{"rendered":"http:\/\/www.neurodegenerationresearch.eu\/?p=4976"},"modified":"2015-05-01T11:06:21","modified_gmt":"2015-05-01T11:06:21","slug":"mouse-models-rarely-mimic-transcriptome-of-human-neurodegeneration-a-systematic-bioinformatics-based-critique","status":"publish","type":"post","link":"https:\/\/neurodegenerationresearch.eu\/sk\/2015\/04\/mouse-models-rarely-mimic-transcriptome-of-human-neurodegeneration-a-systematic-bioinformatics-based-critique\/","title":{"rendered":"Mouse models rarely mimic transcriptome of human neurodegeneration: A systematic bioinformatics-based critique."},"content":{"rendered":"<p><strong><em>Translational research for neurodegenerative disease depends intimately upon animal models. Unfortunately, promising therapies developed using mouse models mostly fail in clinical trials, highlighting uncertainty about how well mouse models mimic human neurodegenerative disease at the molecular level.<\/em><\/strong><\/p>\n<p>This study compared the transcriptional signature of neurodegeneration in mouse models of Alzheimer\u05f3s disease (AD), Parkinson\u05f3s disease (PD), Huntington\u05f3s disease (HD) and amyotrophic lateral sclerosis (ALS) to human disease.<\/p>\n<p>In contrast to aging, which demonstrated a conserved transcriptome between humans and mice, only 3 of 19 animal models showed significant enrichment for gene sets comprising the most dysregulated up- and down-regulated human genes. Spearman\u05f3s correlation analysis revealed even healthy human aging to be more closely related to human neurodegeneration than any mouse model of AD, PD, ALS or HD.<\/p>\n<p>Remarkably, mouse models frequently upregulated stress response genes that were consistently downregulated in human diseases. Among potential alternate models of neurodegeneration, mouse prion disease outperformed all other disease-specific models.<\/p>\n<p>Even among the best available animal models, conserved differences between mouse and human transcriptomes were found across multiple animal model versus human disease comparisons, surprisingly, even including aging. Relative to mouse models, mouse disease signatures demonstrated consistent trends toward preserved mitochondrial function protein catabolism, DNA repair responses, and chromatin maintenance. These findings suggest a more complex and multifactorial pathophysiology in human neurodegeneration than is captured through standard animal models, and suggest that even among conserved physiological processes such as aging, mice are less prone to exhibit neurodegeneration-like changes.<\/p>\n<p>This work may help explain the poor track record of mouse-based translational therapies for neurodegeneration and provides a path forward to critically evaluate and improve animal models of human disease.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Translational research for neurodegenerative disease depends intimately upon animal models. [&hellip;]<\/p>\n<a href=\"https:\/\/neurodegenerationresearch.eu\/sk\/2015\/04\/mouse-models-rarely-mimic-transcriptome-of-human-neurodegeneration-a-systematic-bioinformatics-based-critique\/\">View Post<\/a>","protected":false},"author":3,"featured_media":5002,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[22],"tags":[130,229],"class_list":["post-4976","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research-news","tag-animal-cell-models","tag-translation-research"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.9 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Mouse models rarely mimic transcriptome of human neurodegeneration: A systematic bioinformatics-based critique. - JPND Neurodegenerative Disease Research<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/neurodegenerationresearch.eu\/2015\/04\/mouse-models-rarely-mimic-transcriptome-of-human-neurodegeneration-a-systematic-bioinformatics-based-critique\/\" \/>\n<meta property=\"og:locale\" content=\"sk_SK\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Mouse models rarely mimic transcriptome of human neurodegeneration: A systematic bioinformatics-based critique. - JPND Neurodegenerative Disease Research\" \/>\n<meta property=\"og:description\" content=\"Translational research for neurodegenerative disease depends intimately upon animal models. 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