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Proteins involved in the pathogenesis of Parkinson\u2019s disease (PD), Alzheimer\u2019s disease (AD), and amyotrophic lateral sclerosis (ALS) condensed and underwent ATP-dependent liquid phase separation in vitro. Human inducible pluripotent stem cell\u2013derived neurons from patients with PD and ALS displayed reduced axoplasmic fluidity and decreased intracellular ATP. Last, nicotinamide mononucleotide treatment successfully rescued intracellular ATP levels and axoplasmic viscosity in neurons from patients with PD and ALS and reduced TAR DNA-binding protein 43 (TDP-43) aggregation in human motor neurons derived from a patient with ALS. Thus, our data suggest that the hydrotropic activity of ATP contributes to the regulation of neuronal homeostasis under both physiological and pathological conditions.<\/jats:p>","DOI":"10.1126\/sciadv.adq6077","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T13:58:36Z","timestamp":1745416716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":25,"title":["Loss of intracellular ATP affects axoplasmic viscosity and pathological protein aggregation in mammalian neurons"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9688-0991","authenticated-orcid":true,"given":"Laurent","family":"Guillaud","sequence":"first","affiliation":[{"name":"Molecular Neuroscience Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa, Japan."},{"name":"Cellular and Molecular Synaptic Function Unit, Okinawa Institute 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