{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T06:14:05Z","timestamp":1696313645366},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T00:00:00Z","timestamp":1423094400000},"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":[[2015,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Niemann Pick type C (NPC1) is a rare fatal hereditary cholesterol storage disease associated with a massive Purkinje cells loss. The mechanisms leading to neurodegeneration are still poorly understood. Different laboratories pointed to hypersensitivity to cytotoxic effects of statins (HMG\u2010CoA reductase inhibitors) in NPC1 and suggested an underlying lack of geranylgeranyl pyrophosphate (GGPP). GGPP is a non\u2010sterol isoprenoid essential for cell survival and differentiation. We measured GGPP levels in cerebella of a NPC1 mouse model and of wild\u2010type littermates and found a physiological increase of GGPP levels between post\u2010natal days 21 and 49 in wild\u2010type mice but not in NPC mice. This further supports the hypothesis that Purkinje cell loss may be due to an extremely low level of GGPP. The progressive Purkinje cell loss in NPC starts between p21 and p49. To test the hypothesis, we used long\u2010term organotypic slice cultures of NPC1 mice that display the natural history of NPC1 disease <jats:italic>in vitro<\/jats:italic> and tested if chronic administration of GGPP might prevent Purkinje cell loss. We did not see a beneficial effect. This suggests, in contrast to the expectations, that the relative lack of GGPP may not significantly contribute to mechanisms of Purkinje cell loss in NPC1.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12959-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>We observed a decrease in geranylgeranyl pyrophosphate (GGPP) levels in Niemann Pick type C1 (NPC1) cerebellum and tested the hypothesis that this decrease may lead to Purkinje cell death. Adding GGPP, however, did not prevent Purkinje cell death. The effect of statins, which arrested GGPP production and subsequently augmented Purkinje cell death, however, could be prevented by adding GGPP. Together, this suggested that despite a lower GGPP level in NPC1 cerebellum, this decrease did not cause Purkinje cell death and adding GGPP cannot prevent the natural history of Purkinje cell death in NPC1.<\/jats:p>","DOI":"10.1111\/jnc.12959","type":"journal-article","created":{"date-parts":[[2014,10,15]],"date-time":"2014-10-15T10:35:30Z","timestamp":1413369330000},"page":"153-161","source":"Crossref","is-referenced-by-count":4,"title":["Geranylgeranyl pyrophosphate is crucial for neuronal survival but has no special role in Purkinje cell degeneration in Niemann Pick type C1 disease"],"prefix":"10.1111","volume":"133","author":[{"given":"Nils","family":"Marschalek","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Integrative Neuroanatomie, Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Albert","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Integrative Neuroanatomie, Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Afshordel","sequence":"additional","affiliation":[{"name":"Pharmakologisches Institut f\u00fcr Naturwissenschaftler, Biozentrum, Campus Riedberg Goethe\u2010Universit\u00e4t Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker","family":"Meske","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Integrative Neuroanatomie, Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunter P.","family":"Eckert","sequence":"additional","affiliation":[{"name":"Pharmakologisches Institut f\u00fcr Naturwissenschaftler, Biozentrum, Campus Riedberg Goethe\u2010Universit\u00e4t Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas G.","family":"Ohm","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Integrative Neuroanatomie, Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,2,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1317-11.2011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20248"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"8318","DOI":"10.1523\/JNEUROSCI.23-23-08318.2003","article-title":"The developmental loss of the ability of Purkinje cells to regenerate their axons occurs in the absence of myelin: an in vitro model to prevent myelination","volume":"23","author":"Bouslama\u2010Oueghlani L.","year":"2003","journal-title":"J. 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