{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:49:40Z","timestamp":1791186580938,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2010,2,8]],"date-time":"2010-02-08T00:00:00Z","timestamp":1265587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease and conditions such as ischemic stroke affect millions of individuals annually and exert an enormous financial burden on society. A hallmark of these conditions is the abnormal loss of neurons. Currently, there are no effective strategies to prevent neuronal death in these pathologies. We report that several 2\u2010arylidine and 2\u2010hetarylidin derivatives of the 1,4\u2010benzoxazines class of compounds are highly protective in tissue culture models of neurodegeneration. Results obtained using pharmcalogical inhibitors indicate that neuroprotection by these compounds does not involve the Raf\u2013MEK\u2013ERK or PI\u20103 kinase\u2013Akt signaling pathways nor other survival\u2010promoting molecules such as protein kinase A (PKA), calcium calmodulin kinase A (CaMK), and histone deacetylases (HDACs). We tested one of these compounds, (<jats:italic>Z<\/jats:italic>)\u20106\u2010amino\u20102\u2010(3\u2032,5\u2032\u2010dibromo\u20104\u2032\u2010hydroxybenzylidene)\u20102<jats:italic>H<\/jats:italic>\u2010benzo[b][1,4]oxazin\u20103(4<jats:italic>H<\/jats:italic>)\u2010one, designated as <jats:italic>HSB\u201013<\/jats:italic>, in the 3\u2010nitropropionic acid (3\u2010NP)\u2010induced mouse model of Huntington's disease. HSB\u201013 reduced striatal degeneration and improved behavioral performance in mice administered with 3\u2010NP. Furthermore, HSB\u201013 was protective in a <jats:italic>Drosophila<\/jats:italic> model of amyloid precursor protein (APP) toxicity. To understand how HSB\u201013 and other 1,4\u2010benzoxazines protect neurons, we performed kinase profiling analyses. These analyses showed that HSB\u201013 inhibits GSK3, p38 MAPK, and cyclin\u2010dependent kinases (CDKs). In comparison, another compound, called <jats:italic>ASK\u20102a<\/jats:italic>, that protects cerebellar granule neurons against low\u2010potassium\u2010induced death inhibits GSK3 and p38 MAPK but not CDKs. Despite its structural similarity to HSB\u201013, however, ASK\u20102a is incapable of protecting cortical neurons and HT22 cells against homocysteic acid (HCA)\u2010induced or A\u03b2 toxicity, suggesting that protection against HCA and A\u03b2 depends on CDK inhibition. Compounds described in this study represent a novel therapeutic tool in the treatment of neurodegenerative diseases. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22352","type":"journal-article","created":{"date-parts":[[2010,2,8]],"date-time":"2010-02-08T19:51:54Z","timestamp":1265658714000},"page":"1970-1984","source":"Crossref","is-referenced-by-count":33,"title":["Identification of novel 1,4\u2010benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration"],"prefix":"10.1002","volume":"88","author":[{"given":"Lulu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haribabu","family":"Ankati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashidhar 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