{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:37:42Z","timestamp":1790386662328,"version":"4.1.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,7,19]]},"abstract":"<jats:p>\n                    Emerging genetic and clinical evidence suggests a link between Gaucher disease and the synucleinopathies Parkinson disease and dementia with Lewy bodies. Here, we provide evidence that a mouse model of Gaucher disease (\n                    <jats:italic>\n                      Gba1\n                      <jats:sup>D409V\/D409V<\/jats:sup>\n                    <\/jats:italic>\n                    ) exhibits characteristics of synucleinopathies, including progressive accumulation of proteinase K-resistant \u03b1-synuclein\/ubiquitin aggregates in hippocampal neurons and a coincident memory deficit. Analysis of homozygous (\n                    <jats:italic>\n                      Gba1\n                      <jats:sup>D409V\/D409V<\/jats:sup>\n                    <\/jats:italic>\n                    ) and heterozygous (\n                    <jats:italic>\n                      Gba1\n                      <jats:sup>D409V\/+<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Gba1\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) Gaucher mice indicated that these pathologies are a result of the combination of a loss of glucocerebrosidase activity and a toxic gain-of-function resulting from expression of the mutant enzyme. Importantly, adeno-associated virus-mediated expression of exogenous glucocerebrosidase injected into the hippocampus of\n                    <jats:italic>\n                      Gba1\n                      <jats:sup>D409V\/D409V<\/jats:sup>\n                    <\/jats:italic>\n                    mice ameliorated both the histopathological and memory aberrations. The data support the contention that mutations in\n                    <jats:italic>GBA1<\/jats:italic>\n                    can cause Parkinson disease-like \u03b1-synuclein pathology, and that rescuing brain glucocerebrosidase activity might represent a therapeutic strategy for\n                    <jats:italic>GBA1<\/jats:italic>\n                    -associated synucleinopathies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1108197108","type":"journal-article","created":{"date-parts":[[2011,7,5]],"date-time":"2011-07-05T23:40:37Z","timestamp":1309909237000},"page":"12101-12106","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":286,"title":["CNS expression of glucocerebrosidase corrects \u03b1-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy"],"prefix":"10.1073","volume":"108","author":[{"given":"S. Pablo","family":"Sardi","sequence":"first","affiliation":[{"name":"Genzyme Corporation, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Clarke","sequence":"additional","affiliation":[{"name":"Genzyme Corporation, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathrine","family":"Kinnecom","sequence":"additional","affiliation":[{"name":"Genzyme Corporation, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Tamsett","sequence":"additional","affiliation":[{"name":"Genzyme Corporation, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Li","sequence":"additional","affiliation":[{"name":"Genzyme Corporation, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Stanek","sequence":"additional","affiliation":[{"name":"Genzyme 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