{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:40:57Z","timestamp":1789764057433,"version":"4.0.1"},"reference-count":155,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Glutamate-related excitotoxicity represents a fundamental pathological process underlying both acute and chronic disorders of the central nervous system. Excessive stimulation of ionotropic and metabotropic glutamate receptors induces ionic dysregulation, mitochondrial dysfunction, and oxidative stress, which can activate necrotic and apoptotic pathways, processes further amplified by defective glutamate clearance and astrocytic impairment. These mechanisms are recognized as key contributors to neuronal damage in ischemic stroke, Alzheimer\u2019s disease, Parkinson\u2019s disease, and Huntington\u2019s disease, identifying excitotoxicity as a convergent hallmark of neurodegeneration. Despite considerable progress in elucidating its molecular mechanisms, clinical translation of excitotoxicity-targeted interventions remains limited, largely due to the difficulty of selectively attenuating pathological glutamatergic activity while preserving physiological neurotransmission. Recent advances in nanotechnology, particularly the development of graphene-based materials (GBMs), have offered innovative approaches for neuroprotection. Owing to their unique physicochemical properties and compatibility with neural tissue, GBMs have been investigated as platforms for neural interfacing, regenerative scaffolds, drug delivery platforms, and direct modulators of glutamatergic transmission. In particular, small graphene oxide nanosheets exhibit the capacity to downregulate glutamate release and confer anti-inflammatory and neuroprotective effects. These findings suggest that GBMs may represent a promising class of neuromodulatory tools for mitigating excitotoxic injury, warranting further preclinical and translational investigations.<\/jats:p>","DOI":"10.3390\/life15111776","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T15:03:15Z","timestamp":1763564595000},"page":"1776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Interplay Among Synaptic Glutamate Release and Excitotoxicity: Neuronal Damage and Graphene-Based Materials Related Protection"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9198-8402","authenticated-orcid":false,"given":"Giada","family":"Cellot","sequence":"first","affiliation":[{"name":"Neuroscience Area, International School for Advanced Studies (SISSA), Via Bonomea 265, 34136 Trieste, Italy"},{"name":"Department of Life Sciences, University of Trieste, Via Giorgieri 5, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-0787","authenticated-orcid":false,"given":"Laura","family":"Ballerini","sequence":"additional","affiliation":[{"name":"Neuroscience Area, International School for Advanced Studies (SISSA), Via Bonomea 265, 34136 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1007S","DOI":"10.1093\/jn\/130.4.1007S","article-title":"Glutamate as a neurotransmitter in the brain: Review of physiology and pathology","volume":"130","author":"Meldrum","year":"2000","journal-title":"J. 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