Sustained progression of neuronal cell death causes brain tissue loss and subsequent functional deficits following stroke or central nervous system trauma and in neurodegenerative diseases. Despite obvious differences in the pathology of these neurological disorders, the underlying delayed neuronal demise is carried out by a common biochemical cell death programme. Mitochondrial membrane permeabilization and subsequent release of apoptotic factors are key mechanisms during this process. Bcl-2 family proteins, e.g. the pro-apoptotic Bid, Bax or Bad and the antiapoptotic Bcl-2, Bcl-XL, play a crucial role in the regulation of this mitochondrial checkpoint in neurons. In particular, cleavage of cytosolic Bid and subsequent mitochondrial translocation have been detected in many paradigms of neuronal cell death related to acute or chronic neurodegeneration. The current review focuses on the emerging role of Bid as an integrating key regulator of the intrinsic death pathway that amplifies caspase-dependent and caspase-independent execution of neuronal apoptosis. Therefore pharmacological inhibition of Bid provides a promising therapeutic strategy in neurological diseases where programmed cell death is prominent.
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December 2006
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Conference Article|
October 25 2006
Targeting Bid to prevent programmed cell death in neurons
C. Culmsee;
C. Culmsee
1
*Pharmaceutical Biology–Biotechnology, Department of Pharmacy, Ludwig-Maximilians-University, Butenandtstrasse 5-13, Building D, D-81377 Munich, Germany
1To whom correspondence should be addressed (email carsten.culmsee@cup.uni-muenchen.de).
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N. Plesnila
N. Plesnila
†Department of Neurosurgery, University of Munich Medical Center – Grosshadern, Marchioninistrasse 27, D-81377 Munich, Germany
‡Institute for Surgical Research, University of Munich Medical Center – Grosshadern, Marchioninistrasse 27, D-81377 Munich, Germany
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Publisher: Portland Press Ltd
Received:
July 19 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (6): 1334–1340.
Article history
Received:
July 19 2006
Citation
C. Culmsee, N. Plesnila; Targeting Bid to prevent programmed cell death in neurons. Biochem Soc Trans 1 December 2006; 34 (6): 1334–1340. doi: https://doi.org/10.1042/BST0341334
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