![\"NAD\u207a](\"https:\/\/www.europesays.com\/us\/wp-content\/uploads\/2025\/11\/nad-restores-memory-in.jpg\" "\\"NR")
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NR induces transcription of genes involved in axon development, oxygen metabolism, mitochondrion localization, and autophagy in tauopathy mice. GO terms enriched in each of the eight classes of clusters in (A); each circular bar graph represents one cluster or class of clusters, and bar length correlates with the number of DEGs represented. GO terms shown in red font relate to mRNA. Clusters 4 and 5 are similar and are grouped together. Class 1 includes clusters 1, 2, and 6 marked with red. Class 2 includes clusters 4 and 5 marked with orange. Class 3 includes cluster 8 marked with yellow. GTPase, guanosine triphosphatase; NAD(P)H, reduced form of NAD phosphate; IRES, internal ribosomal entry site; GTP, guanosine 5\u2032-triphosphate; MHC, major histocompatibility complex. Credit: Science Advances (2025). DOI: 10.1126\/sciadv.ady9811<\/p>\n
Alzheimer’s disease (AD), the leading cause of dementia, affects nearly 40 million individuals globally, resulting in a gradual loss of memory and independence. Despite extensive research over the past decades, no treatments have been found that can halt or reverse the progression of this devastating disease.<\/p>\n
In AD, a major contributor to neuronal dysfunction is the protein tau<\/a>. Tau typically plays a crucial role in keeping the internal structure of neurons stable, much like train tracks help trains stay on course. However, in some diseases, tau undergoes abnormal modifications and starts to aggregate, disrupting this transport system, thus leading to neuronal damage and subsequent memory loss.<\/p>\n An international team of researchers has reported a new mechanism by which boosting the natural metabolite NAD\u207a can protect the brain from the degeneration associated with AD. Their paper, titled “NAD\u207a reverses Alzheimer’s neurological deficits via regulating differential alternative RNA splicing of EVA1C,” is published<\/a> in Science Advances.<\/p>\n The team is led by Associate Professor Evandro Fei Fang from the University of Oslo and Akershus University Hospital, Norway, in collaboration with Professor Oscar Junhong Luo from Jinan University, China, and Associate Professor Joana M. Silva from the University of Minho, Portugal.<\/p>\n How NAD\u207a supports brain health<\/p>\n NAD\u207a (nicotinamide adenine dinucleotide<\/a>, oxidized form) is a vital metabolite involved in energy metabolism and neuronal resilience in the body. It normally declines with age and especially in various neurodegenerative diseases.<\/p>\n “Preliminary studies have shown that supplementation with NAD\u207a precursors, such as nicotinamide riboside<\/a> (NR) or nicotinamide mononucleotide (NMN), can offer therapeutic benefits in AD animal models and early clinical trials. However, the molecular mechanisms<\/a> behind these benefits remain largely unclear,” first author Alice Ruixue Ai says.<\/p>\n The new study reveals that NAD\u207a works through a previously unidentified RNA-splicing pathway. This pathway is regulated by a protein called EVA1C, which plays an essential role in the process of RNA splicing. RNA splicing allows a single gene<\/a> to produce multiple isoforms of a protein, and one isoform may show distinctive effects from the other isoforms. Its dysregulation is one of the most recently acknowledged risk factors for AD.<\/p>\n The researchers discovered that when NAD\u207a levels are increased, EVA1C helps correct mistakes in RNA splicing. This restoration process improves the function of hundreds of genes, many crucial for brain health, which can help reverse the neurodegenerative damage caused by tau.<\/p>\n Cross-species validation from worms to mice to the human brain<\/p>\n To demonstrate the impact of this mechanism, the researchers used a comprehensive approach that included computer predictions and validation in different animal models, including worms, mice, as well as human brain samples.<\/p>\n They first identified age-related changes in RNA splicing in a specific type of worm. They found that adding NAD\u207a could correct the splicing issues caused by the toxic tau protein. In mice with tau-related mutations, NAD\u207a supplements improved RNA splicing, restored brain function, and enhanced memory performance.<\/p>\n “Notably, we found when the EVA1C gene was knocked down, these benefits were lost, confirming that EVA1C is essential for NAD\u207a-mediated neuroprotection,” Associate Professor Evandro Fei Fang-Stavem says.<\/p>\n Aligned with these animal studies, EVA1C levels were significantly reduced in brain cells from people with early AD.<\/p>\n Using AI to uncover the mechanism<\/p>\n To further investigate how EVA1C works, the team used an AI-driven platform to predict how proteins interact with one another, analyzing structural, sequential, and evolutionary data from millions of proteins.<\/p>\n This analysis revealed that NAD\u207a promotes a specific form of EVA1C that efficiently binds to essential proteins, which are central to protein folding and clearance. This connection links metabolic homeostasis, RNA splicing processes and protein management, three processes that are critically impaired in AD.<\/p>\n Towards new Alzheimer’s treatments<\/p>\n By establishing the connection between NAD\u207a and EVA1C, this study lays the groundwork for the development of new therapies and optimization of NAD\u207a augmentation strategies in humans.<\/p>\n “We propose that maintaining NAD\u207a levels could help preserve neuronal identity and delay cognitive decline<\/a>, paving the way for combination treatments to enhance RNA splicing,” Ai says.<\/p>\n More information:<\/strong> \t\t\t\t\t\t\t\t\t\t\t\tProvided by \t\t\t\t\t\t\t\t\t\t\t\t\t<\/a><\/p>\n \n Citation<\/strong>: \n This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
\n Ruixue Ai et al, NAD+reverses Alzheimer’s neurological deficits via regulating differential alternative RNA splicing of EVA1C, Science Advances (2025). DOI: 10.1126\/sciadv.ady9811<\/a><\/p>\n
\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\tUniversity of Oslo<\/a>
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\n NAD\u207a restores memory in Alzheimer’s disease models by correcting RNA errors (2025, November 10)
\n retrieved 11 November 2025
\n from https:\/\/medicalxpress.com\/news\/2025-11-nad-memory-alzheimer-disease-rna.html\n <\/p>\n
\n part may be reproduced without the written permission. The content is provided for information purposes only.\n <\/p>\n","protected":false},"excerpt":{"rendered":"NR induces transcription of genes involved in axon development, oxygen metabolism, mitochondrion localization, and autophagy in tauopathy mice.…\n","protected":false},"author":3,"featured_media":370797,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11],"tags":[210,1212,1211,1213,1210,1209,1214,67,132,68],"class_list":{"0":"post-370796","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-health","9":"tag-health-research","10":"tag-health-research-news","11":"tag-health-science","12":"tag-medicine-research","13":"tag-medicine-research-news","14":"tag-medicine-science","15":"tag-united-states","16":"tag-unitedstates","17":"tag-us"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/115529315080301758","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/370796","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=370796"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/370796\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/370797"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=370796"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=370796"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=370796"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}