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Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. These\n                    <jats:italic>Srf<\/jats:italic>\n                    <jats:sup>GFAP-ER<\/jats:sup>\n                    CKO astrocytes do not affect neuron survival, synapse numbers, synaptic plasticity or learning and memory. However, the brains of\n                    <jats:italic>Srf<\/jats:italic>\n                    knockout mice exhibited neuroprotection against kainic-acid induced excitotoxic cell death. Relevant to human neurodegenerative diseases,\n                    <jats:italic>Srf<\/jats:italic>\n                    <jats:sup>GFAP-ER<\/jats:sup>\n                    CKO astrocytes abrogate nigral dopaminergic neuron death and reduce \u03b2-amyloid plaques in mouse models of Parkinson\u2019s and Alzheimer\u2019s disease, respectively. Taken together, these findings establish SRF as a key molecular switch for the generation of reactive astrocytes with neuroprotective functions that attenuate neuronal injury in the setting of neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.7554\/elife.95577","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T08:40:06Z","timestamp":1706604006000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.95577","source":"Crossref","is-referenced-by-count":2,"title":["SRF-deficient astrocytes provide neuroprotection in mouse models of excitotoxicity and neurodegeneration"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2089-9792","authenticated-orcid":true,"given":"Surya Chandra Rao","family":"Thumu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dese585","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Neuroscience, Indian Institute of Science","place":["Bangalore, 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