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Based on these observations and reduced NAD\n                    <jats:sup>+<\/jats:sup>\n                    in muscles of SBMA mouse models, we tested the therapeutic potential of NAD\n                    <jats:sup>+<\/jats:sup>\n                    restoration in vivo by treating postsymptomatic transgenic SBMA mice with the NAD\n                    <jats:sup>+<\/jats:sup>\n                    precursor nicotinamide riboside (NR). NR supplementation failed to alter disease progression and had no effect on increasing NAD\n                    <jats:sup>+<\/jats:sup>\n                    or ATP content in muscle, despite producing a modest increase of NAD\n                    <jats:sup>+<\/jats:sup>\n                    in the spinal cords of SBMA mice. Metabolomic and proteomic profiles of SBMA quadriceps muscles indicated alterations in several important energy-related pathways that use NAD\n                    <jats:sup>+<\/jats:sup>\n                    , in addition to the NAD\n                    <jats:sup>+<\/jats:sup>\n                    salvage pathway, which is critical for NAD\n                    <jats:sup>+<\/jats:sup>\n                    regeneration for use in cellular energy production. We also observed decreased mRNA levels of nicotinamide riboside kinase 2 (\n                    <jats:italic>Nmrk2<\/jats:italic>\n                    ), which encodes a key kinase responsible for NR phosphorylation, allowing its use by the NAD\n                    <jats:sup>+<\/jats:sup>\n                    salvage pathway. Together, these data suggest a model in which NAD\n                    <jats:sup>+<\/jats:sup>\n                    levels are significantly decreased in muscles of an SBMA mouse model and intransigent to NR supplementation because of decreased levels of\n                    <jats:italic>Nmrk2<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.178048","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T14:14:57Z","timestamp":1709820897000},"source":"Crossref","is-referenced-by-count":7,"title":["Differentially disrupted spinal cord and muscle energy metabolism in spinal and bulbar muscular atrophy"],"prefix":"10.1172","volume":"9","author":[{"given":"Danielle","family":"DeBartolo","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, 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