Abstract
Neuronal cell death is a key feature of both normal nervous system development and neuropathological conditions. The Bcl-2 family, via its regulation of both caspase-dependent and caspase-independent cell death pathways, is uniquely positioned to critically control neuronal cell survival. Targeted gene disruptions of specific bcl-2 family members and the generation of transgenic mice overexpressing anti- or pro-apoptotic Bcl-2 family members have confirmed the importance of the Bcl-2 family in the nervous system. Data from studies of human brain tissue and experimental animal models of neuropathological conditions support the hypothesis that the Bcl-2 family regulates cell death in the mature nervous system and suggest that pharmacological manipulation of Bcl-2 family action could prove beneficial in the treatment of human neurological conditions such as stroke and neurodegenerative diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 189-203 |
| Number of pages | 15 |
| Journal | Biochimica et Biophysica Acta - Molecular Cell Research |
| Volume | 1644 |
| Issue number | 2-3 |
| DOIs | |
| State | Published - Mar 1 2004 |
| Externally published | Yes |
Funding
We wish to thank our many colleagues in the cell death field for stimulating discussions on the role of the Bcl-2 family in neuronal cell death regulation. We gratefully acknowledge the technical contributions of Barbara Klocke and Cecelia Latham to the work performed in our laboratory and discussed in this review. We also thank Jo Self and Angela Schmeckebier for assistance in preparation of this manuscript. KAR is supported by NIH Grants 35107 and 41962. RSA received support from the UAB Medical Scientist Training Program (TM GM0831). JMN received support from the Research Institute of the Children's Hospital of Alabama and the Dixon Foundation.
Keywords
- Apoptosis
- Bax
- Bcl-X
- Caspase
- Neuropathology
- Programmed cell death
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
