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Bim Is Elevated in Alzheimer's Disease Neurons and Is Required for β-Amyloid-Induced Neuronal Apoptosis.
- Source :
-
Journal of Neuroscience . 1/24/2007, Vol. 27 Issue 4, p893-900. 8p. 1 Diagram, 6 Graphs. - Publication Year :
- 2007
-
Abstract
- The molecules that mediate neuron death in Alzheimer's disease (AD) are largely unknown. We report that β-amyloid (Aβ), a death-promoting peptide implicated in the pathophysiology of AD, induces the proapoptotic protein Bcl-2 interacting mediator of cell death (Bim) in cultured hippocampal and cortical neurons. We further find that Bim is an essential mediator of Aβ-induced neurotoxicity. Our examination of postmortem AD human brains additionally reveals upregulation of Bim in vulnerable entorhinal cortical neurons, but not in cerebellum, a region usually unaffected by AD. Accumulating evidence links inappropriate induction/activation of cell cycle-related proteins to AD, but their roles in the disease have been unclear. We find that the cell cycle molecule cyclin-dependent kinase 4 (cdk4) and its downstream effector B-myb, are required for Aβ-dependent Bim induction and death in cultured neurons. Moreover, neurons that overexpress Bim in AD brains also show elevated levels of the cell cycle-related proteins cdk4 and phospho-Rb. Our observations indicate that Bim is a proapoptotic effector of Aβ and of dysregulated cell cycle proteins in AD and identify both Bim and cell cycle elements as potential therapeutic targets. [ABSTRACT FROM AUTHOR]
- Subjects :
- *APOPTOSIS
*CELL cycle
*ALZHEIMER'S disease
*NEUROPEPTIDES
*NEURONS
*NEUROTOXICOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 02706474
- Volume :
- 27
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 23862068
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.3524-06.2007