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Due its key role in oxidative metabolism, antioxidant defence and neurotransmitter synthesis, copper is particularly important for neuronal development and proper neuronal function. Moreover, increasing evidence suggests that copper also serves important functions in synaptic and network activity, the regulation of circadian rhythms, and arousal. However, it is important to note that because of copper's ability to redox cycle and generate reactive species, cellular levels of the metal must be tightly regulated to meet cellular needs while avoiding copper\u2010induced oxidative stress. Therefore, it is essential that the intricate system of copper transporters, exporters, copper chaperones and copper trafficking proteins function properly and in coordinate fashion. Indeed, disorders of copper metabolism such as Menkes disease and Wilson disease, as well as diseases linked to dysfunction of copper\u2010requiring enzymes, such as SOD1\u2010linked amyotrophic lateral sclerosis, demonstrate the dramatic neurological consequences of altered copper homeostasis. In this review, we explore the physiological importance of copper in the nervous system as well as pathologies related to improper copper handling.\n                  <\/jats:p>","DOI":"10.1111\/ejn.16370","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T03:57:47Z","timestamp":1715745467000},"page":"3505-3543","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["The physiological and pathophysiological roles of copper in the nervous system"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2727-9497","authenticated-orcid":false,"given":"Jenna","family":"Gale","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Pittsburgh Institute for Neurodegenerative Diseases University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania 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