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Without a healthy MT system, motor neurons (MN) function at sub-optimal levels and die. In addition, other effects of ALS, like axon\/dendrite degeneration, may occur from a pathophysiological cascade spurred by MT dysfunction. A phenotypic screen identified Dipyridamole (DPM), an FDA-approved and safe drug, as having extraordinary effects on ALS patient induced pluripotent stem cell (iPSC)-derived MNs. The drug prevented MT fragmentation, loss of MT content, impaired MT bioenergetics, axon\/dendrite degeneration, and premature MN death, extending neuronal survival by more than fivefold. Importantly, its efficacy extended across iPSC-derived neurons representing two different familial forms of ALS (C9orf72, TDP43) and Alzheimer\u2019s disease (PSEN1), implying broad neuroprotection across ALS forms and other neurodegenerative diseases. DPM increased MT respiration and pyruvate uptake in a mechanism requiring the Mitochondrial Pyruvate Carrier (MPC), mechanistically explaining its biological activities. Thus, DPM is a promising drug to repurpose or refine for treating neurodegenerative diseases or other diseases that would benefit by augmenting pyruvate uptake into MT.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Teaser<\/jats:title>\n                  <jats:p>Dipyridamole, an FDA-approved drug, restores mitochondrial function and protects neurons in ALS and Alzheimer\u2019s disease.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.30.722019","type":"posted-content","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T15:20:13Z","timestamp":1777994413000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological rescue of mitochondrial dysfunction, neurite degeneration, and premature death of ALS and AD iPSC-derived neurons"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1907-4811","authenticated-orcid":false,"given":"Neelam","family":"Shahani","sequence":"first","affiliation":[{"name":"Department 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