GDNF protects against aluminum-induced apoptosis in rabbits by upregulating Bcl-2 and Bcl-XL and inhibiting mitochondrial Bax translocation

Othman Ghribi, Mary M. Herman, Michael S. Forbes, David A. DeWitt, John Savory

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)764-773
Number of pages10
JournalNeurobiology of Disease
Issue number5
StatePublished - 2001
Externally publishedYes


  • Aluminum
  • Bax
  • Bcl-2
  • Caspase-3
  • Cytochrome c
  • Endoplasmic reticulum
  • GDNF

ASJC Scopus subject areas

  • Neurology

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