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Article
GDNF Protects against Aluminum-Induced Apoptosis in Rabbits by Upregulating Bcl-2 and Bcl-XL and Inhibiting Mitochondrial Bax Translocation
Faculty Publications and Presentations
  • David A. Dewitt, Liberty University
  • Othman Ghribi
  • Mary M. Herman
  • Michael S. Forbes
  • John Savory
Publication Date
1-1-2001
Comments
Published in Neurobiology of Disease 8, 764–773 (2001).
Abstract
Direct (intracisternal) injection of aluminum complexes into rabbit brain results in a number of similarities with the neuropathological and biochemical changes observed in Alzheimer’s disease and provides the opportunity to assess early events in neurodegeneration. This mode of administration induces cytochrome c release from mitochondria, a decrease in Bcl-2 in both mitochondria and endoplasmic reticulum, Bax translocation into mitochondria, activation of caspase-3, and DNA fragmentation. Coadministration of glial cell neuronal-derived factor (GDNF) inhibits these Bcl-2 and Bax changes, upregulates Bcl-XL, and abolishes the caspase-3 activity. Furthermore, treatment with GDNF dramatically inhibits apoptosis, as assessed by the TUNEL technique for detecting DNA damage. Treatment with GDNF may represent a therapeutic strategy to reverse the neuronal death associated with Alzheimer’s disease and may exert its effect on apoptosis-regulatory proteins.
Citation Information
David A. Dewitt, Othman Ghribi, Mary M. Herman, Michael S. Forbes, et al.. "GDNF Protects against Aluminum-Induced Apoptosis in Rabbits by Upregulating Bcl-2 and Bcl-XL and Inhibiting Mitochondrial Bax Translocation" (2001)
Available at: http://works.bepress.com/david_dewitt/1/