{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:48:07Z","timestamp":1787021287396,"version":"build-2736575974"},"reference-count":53,"publisher":"The Company of Biologists","issue":"12","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35NS105076"],"award-info":[{"award-number":["R35NS105076"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. 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We show that human induced pluripotent stem cell (hiPSC)-derived motor neurons and sensory neurons provide a model system for the study of bortezomib-induced peripheral neuropathy, with promising implications for furthering the mechanistic understanding of and developing treatments for preventing axonal damage. Human neurons in tissue culture displayed distal-to-proximal neurite degeneration when exposed to bortezomib. This process coincided with disruptions in mitochondrial function and energy homeostasis, similar to those described in rodent models of bortezomib-induced neuropathy. Moreover, although the degenerative process was unaffected by inhibition of caspases, it was completely blocked by exogenous nicotinamide adenine dinucleotide (NAD+), a mediator of the SARM1-dependent axon degeneration pathway. We demonstrate that bortezomib-induced neurotoxicity in relevant human neurons proceeds through mitochondrial dysfunction and NAD+ depletion-mediated axon degeneration, raising the possibility that targeting these changes might provide effective therapeutics for the prevention of bortezomib-induced neuropathy and that modeling chemotherapy-induced neuropathy in human neurons has utility.<\/jats:p>","DOI":"10.1242\/dmm.049358","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T04:30:04Z","timestamp":1668745804000},"source":"Crossref","is-referenced-by-count":20,"title":["Bortezomib-induced neurotoxicity in human neurons is the consequence of nicotinamide adenine dinucleotide depletion"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9185-5765","authenticated-orcid":false,"given":"Andrew R.","family":"Snavely","sequence":"first","affiliation":[{"name":"F.M. 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