{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:28:39Z","timestamp":1791808119171,"version":"4.3.4"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,9,26]]},"abstract":"<jats:p>\n                    Sandhoff disease is a lysosomal storage disorder characterized by\n the absence of \u03b2-hexosaminidase and storage of G\n                    <jats:sub>M2<\/jats:sub>\n                    ganglioside and related glycolipids in the central nervous system. The\n glycolipid storage causes severe neurodegeneration through a poorly\n understood pathogenic mechanism. In symptomatic Sandhoff disease mice,\n apoptotic neuronal cell death was prominent in the caudal\n regions of the brain. cDNA microarray analysis to monitor gene\n expression during neuronal cell death revealed an upregulation of\n genes related to an inflammatory process dominated by activated\n microglia. Activated microglial expansion, based on gene expression and\n histologic analysis, was found to precede massive neuronal death.\n Extensive microglia activation also was detected in a human case of\n Sandhoff disease. Bone marrow transplantation of Sandhoff disease mice\n suppressed both the explosive expansion of activated microglia and the\n neuronal cell death without detectable decreases in neuronal\n G\n                    <jats:sub>M2<\/jats:sub>\n                    ganglioside storage. These results suggest a mechanism\n of neurodegeneration that includes a vigorous inflammatory response as\n an important component. Thus, this lysosomal storage disease has\n parallels to other neurodegenerative disorders, such as Alzheimer's\n and prion diseases, where inflammatory processes are believed to\n participate directly in neuronal cell death.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.20.10954","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"10954-10959","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":354,"title":["Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation"],"prefix":"10.1073","volume":"97","author":[{"given":"Ryuichi","family":"Wada","sequence":"first","affiliation":[{"name":"Genetics of Development and Disease Branch, National Institute of\r Diabetes and Digestive and Kidney Diseases, National Institutes of\r Health, Bethesda, MD 20892; and Department of Medical\r Genetics, Children's National Medical Center, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia J.","family":"Tifft","sequence":"additional","affiliation":[{"name":"Genetics of Development and Disease Branch, National Institute of\r Diabetes and Digestive and Kidney Diseases, National Institutes of\r Health, Bethesda, MD 20892; and Department of Medical\r Genetics, Children's National Medical Center, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Proia","sequence":"additional","affiliation":[{"name":"Genetics of Development and Disease Branch, National Institute of\r Diabetes and Digestive and Kidney Diseases, National Institutes of\r Health, Bethesda, MD 20892; and Department of Medical\r Genetics, Children's National Medical Center, Washington, DC 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