{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:12:18Z","timestamp":1791886338124,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,7,10]],"date-time":"2012-07-10T00:00:00Z","timestamp":1341878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>J. Neurochem.<\/jats:italic>(2012)<jats:bold>122<\/jats:bold>, 752\u2013763.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Factors released from injured dopaminergic (DA) neurons may trigger microglial activation and set in motion a vicious cycle of neuronal injury and inflammation that fuels progressive DA neurodegeneration in Parkinson\u2019s disease. In this study, using proteomic and immunoblotting analysis, we detected elevated levels of cystatin C in conditioned media (CM) from 1\u2010methyl\u20104\u2010phenylpyridinium and dieldrin\u2010injured rat DA neuronal cells. Immunodepletion of cystatin C significantly reduced the ability of DA neuronal CM to induce activation of rat microglial cells as determined by up\u2010regulation of inducible nitric oxide synthase, production of free radicals and release of proinflammatory cytokines as well as activated microglia\u2010mediated DA neurotoxicity. Treatment of the cystatin C\u2010containing CM with enzymes that remove O\u2010 and sialic acid\u2010, but not N\u2010linked carbohydrate moieties markedly reduced the ability of the DA neuronal CM to activate microglia. Taken together, these results suggest that DA neuronal cystatin C plays a role in the neuronal injury\u2010induced microglial activation and neurotoxicity. These findings from the rat DA neuron\u2010microglia<jats:italic>in vitro<\/jats:italic>model may help guide continued investigation to define the precise role of cystatin C in the complex interplay among neurons and glia in the pathogenesis of Parkinson\u2019s disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2012.07826.x","type":"journal-article","created":{"date-parts":[[2012,6,9]],"date-time":"2012-06-09T14:11:46Z","timestamp":1339251106000},"page":"752-763","source":"Crossref","is-referenced-by-count":38,"title":["Involvement of dopaminergic neuronal cystatin C in neuronal injury\u2010induced microglial activation and neurotoxicity"],"prefix":"10.1111","volume":"122","author":[{"given":"Garima","family":"Dutta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Barber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Doperalski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,7,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)80695-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfm210"},{"key":"e_1_2_7_4_1","first-page":"1363","article-title":"The cystatins: a diverse superfamily of cysteine peptidase inhibitors","volume":"45","author":"Barrett A. 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