{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:15:52Z","timestamp":1773278152928,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2002,8,5]],"date-time":"2002-08-05T00:00:00Z","timestamp":1028505600000},"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":[[2002,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gene therapy for neurodegenerative diseases may utilize the expression of neurotrophic factors because of their potential to promote survival and regeneration of injured neuronal cells. Increasing numbers of these factors are being considered for gene transfer, but their specificity and efficacy in neuroprotection are greatly variable. The major aims of this study were to carry out gene transfer of various neurotrophic factors and investigate their mechanisms of action as well as their protective effects on the viability of rat pheochromocytoma (PC12) cells. We used glutamate, S\u2010nitroso\u2010N\u2010acetyl\u2010DL\u2010penicillamine (SNAP), and staurosporine to induce excitatory damage, oxidative stress, and apoptosis, respectively, because these mechanisms are thought to participate in various disease processes leading to degeneration of cells. We utilized adenovirus vectors for efficient gene transfer of trophic factors (glial\u2010cell derived neurotrophic factor [GDNF] and cardiotrophin\u20101 [CT\u20101]) or calbindin\u2010D28k. We found that GDNF and CT\u20101 gene transfers were equally effective in saving PC12 cells from injury, but calbindin expression did not show any beneficial effects. GDNF gene transfer was much more efficient in protecting PC12 cells from damage than direct GDNF administration. The protection by GDNF expression against staurosporine was mediated through both phosphatidylinositol 3\u2010kinase (PI3K) and mitogen\u2010activated protein kinase kinase (MAPK kinase; MEK) pathways, but only the MEK pathway was involved in the protection against SNAP. In contrast, the protective effect of GDNF against glutamate toxicity was independent of these RET\u2010dependent signal transduction pathways. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.10358","type":"journal-article","created":{"date-parts":[[2002,9,5]],"date-time":"2002-09-05T20:29:28Z","timestamp":1031257768000},"page":"622-632","source":"Crossref","is-referenced-by-count":15,"title":["Gene transfer of glial cell\u2010derived neurotrophic factor and cardiotrophin\u20101 protects PC12 cells from injury: Involvement of the phosphatidylinositol 3\u2010kinase and mitogen\u2010activated protein kinase kinase pathways"],"prefix":"10.1002","volume":"69","author":[{"given":"Gabor","family":"Toth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huibin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roumen 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