Regulation of Cell Death by the Bcl-2 Family of Proteins

  • Yoshihide Tsujimoto
Part of the Advances in Behavioral Biology book series (ABBI, volume 53)


One of the promising approaches for the treatment or prevention of neurodegenerative diseases, including Parkinson’s disease, is to investigate the molecular basis of neurodegeneration or neuronal death and elucidate possible therapeutic molecular targets. The Bcl-2 family of proteins is a major cell death regulator and is implicated in determining the survival or death of neurons under physiological as well as pathological conditions. I will provide an overview of the functions of this family of proteins and their targets, and will discuss a possible molecular approach for the prevention of neurodegenerative diseases.


Spinal Muscular Atrophy Necrotic Cell Death Spinal Muscular Atrophy Patient Necrotic Death Therapeutic Molecular Target 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Refernces (our works cited)

  1. 1.
    Tsujimoto, Y. Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria. Genes to Cells 3:697–707, 1998PubMedCrossRefGoogle Scholar
  2. 2.
    Tsujimoto, Y. and Shimizu, S.: Bcl-2 family: Life-or-death switch, FEBS lett. 466: 6–10, 2000PubMedCrossRefGoogle Scholar
  3. 3.
    Tsujimoto, Y Prevention of neuronal cell death by Bcl-2. Results Probi. Cell Differ. 24: 137–55, 1998Google Scholar
  4. 4.
    Iwahashi, H., Eguchi, Y, Yasuhara, N., Hanafusa, T., Matsuzawa, Y and Tsujimoto, Y: Synergistic antiapoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy. Nature 390: 413–417, 1997PubMedCrossRefGoogle Scholar
  5. 5.
    Shimizu, S., Eguchi, Y, Kamiike, W., Waguri, S., Uchiyama, Y, Matsuda, H. and Tsujimoto, Y: Retardation of chemical hypoxia-induced necrotic cell death by Bcl-2 and ICE inhibitors: Possible common steps in apoptosis and necrosis. Oncogene 12: 2045–2050, 1996.PubMedGoogle Scholar
  6. 6.
    Eguchi, Y, Shimizu, S. and Tsujimoto, Y: Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res. 57: 1835–1840, 1997PubMedGoogle Scholar
  7. 7.
    Eguchi, Y, Srinivasan, A., Tomaselli, K. J., Shimizu, S. and Tsujimoto Y, ATP-dependent steps in apoptotic signal transduction. Cancer Res. 59: 2174–2181, 1999PubMedGoogle Scholar
  8. 8.
    Shimizu, S., Narita, M. and Tsujimoto T, Y Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 399: 483–487, 1999PubMedCrossRefGoogle Scholar
  9. 9.
    Tsujimoto, Y. and Shimizu, S. VDAC regulation by the Bcl-2 family of proteins. Cell Death Diff. 7: 1174–1181,2000CrossRefGoogle Scholar
  10. 10.
    Shimizu, S., Shinohara, Y. and Tsujimoto, Y. Bax and Bcl-xL independently regulate apoptotic changes of yeast mitochondria that require VDAC but not adenine nucleotide translocator. Oncogene 19: 4309–4318, 2000PubMedCrossRefGoogle Scholar
  11. 11.
    Shimizu, S., Matsuoka, Y, Shinohara, Y, Yoneda, Yand Tsujimoto, Y Essential role of voltage-dependent anion channel in various forms of apoptosis in mammalian cells. J. Cell Biol. 152: 237–250 (2001)PubMedCrossRefGoogle Scholar
  12. 12.
    Shimizu, S., Konishi, A., Kodama, T. and Tsujimoto, Y.: BH4 domain of anti-apoptotic Bcl-2 family members closes VDAC, and inhibits apoptotic mitochondrial changes and cell death. Proc. Natl. Acad. Sci. USA 97: 3100–3105, 2000PubMedCrossRefGoogle Scholar
  13. 13.
    Kusano, H., Shimizu, S., Koya, R.-C, Fujita, H., Kamada, S., Kuzumaki, N. and Tsujimoto Y, Y Human gelsolin prevents apoptosis by inhibiting apoptotic mitochondrial changes via closing VDAC. Oncogene 19: 4807–4814, 2000PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Yoshihide Tsujimoto
    • 1
  1. 1.Lab. Molecular GeneticsOsaka University Graduate School of MedicineSuita, OsakaJapan

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