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However, current research on neuroprotection primarily focuses on functional and behavioral assessments. The impact of neuroprotective interventions on neurotransmission, a critical function of the central nervous system (CNS), remains relatively underexplored. In this study, we report the first direct evidence for neuroprotective effect on neurochemical transmission by multi\u2010spatiotemporal electrochemistry. We employed in vivo and single\u2010vesicle electrochemistry to quantitatively evaluate the neuroprotective effect of an antioxidative Fe single\u2010atom nanozyme (Fe\n                    <jats:sub>1<\/jats:sub>\n                    \/NC SAzyme) on neurotransmission, using a 1\u2010methyl\u20104\u2010phenylpyridinium (MPP\n                    <jats:sup>+<\/jats:sup>\n                    )\u2010induced Parkinson's disease (PD) model. In the PD animal model, Fe\n                    <jats:sub>1<\/jats:sub>\n                    \/NC SAzyme mitigates MPP\n                    <jats:sup>+<\/jats:sup>\n                    neurotoxicity by decreasing damage to dopaminergic neurons, increasing evoked dopamine release, attenuating spontaneous firing, and alleviating locomotor impairment. At the single\u2010cell level, pretreatment with Fe\n                    <jats:sub>1<\/jats:sub>\n                    \/NC SAzyme inhibits MPP\n                    <jats:sup>+<\/jats:sup>\n                    effects by scavenging reactive oxygen species (ROS), increasing cell viability and ATP concentration, and enhancing the exocytotic release. This study not only provides a research paradigm for directly quantifying therapeutic mechanisms of brain disorders and injury but also reinforces a novel neuroprotective strategy through modulating the redox homeostasis with biocatalytic reactions.\n                  <\/jats:p>","DOI":"10.1002\/anie.202502163","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T04:23:53Z","timestamp":1742185433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Direct Quantification of Neuroprotective Effect of Single\u2010Atom Catalyst on Neurochemical Transmission by Multi\u2010Spatiotemporal Electrochemistry"],"prefix":"10.1002","volume":"64","author":[{"given":"Wenjie","family":"Ma","sequence":"first","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences Key Laboratory of Analytical Chemistry for Living Biosystems Institute of Chemistry The Chinese Academy of Sciences 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