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Bim is elevated in Alzheimer's disease neurons and is required for beta-amyloid-induced neuronal apoptosis.
J Neurosci 2007; 27(4):893-900JN

Abstract

The molecules that mediate neuron death in Alzheimer's disease (AD) are largely unknown. We report that beta-amyloid (Abeta), 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 Abeta-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 Abeta-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 Abeta and of dysregulated cell cycle proteins in AD and identify both Bim and cell cycle elements as potential therapeutic targets.

Authors+Show Affiliations

Department of Pathology, Center for Neurobiology and Behavior and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. scb34@columbia.edu

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17251431

Citation

Biswas, Subhas C., et al. "Bim Is Elevated in Alzheimer's Disease Neurons and Is Required for Beta-amyloid-induced Neuronal Apoptosis." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 27, no. 4, 2007, pp. 893-900.
Biswas SC, Shi Y, Vonsattel JP, et al. Bim is elevated in Alzheimer's disease neurons and is required for beta-amyloid-induced neuronal apoptosis. J Neurosci. 2007;27(4):893-900.
Biswas, S. C., Shi, Y., Vonsattel, J. P., Leung, C. L., Troy, C. M., & Greene, L. A. (2007). Bim is elevated in Alzheimer's disease neurons and is required for beta-amyloid-induced neuronal apoptosis. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 27(4), pp. 893-900.
Biswas SC, et al. Bim Is Elevated in Alzheimer's Disease Neurons and Is Required for Beta-amyloid-induced Neuronal Apoptosis. J Neurosci. 2007 Jan 24;27(4):893-900. PubMed PMID: 17251431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bim is elevated in Alzheimer's disease neurons and is required for beta-amyloid-induced neuronal apoptosis. AU - Biswas,Subhas C, AU - Shi,Yijie, AU - Vonsattel,Jean-Paul G, AU - Leung,Conrad L, AU - Troy,Carol M, AU - Greene,Lloyd A, PY - 2007/1/26/pubmed PY - 2007/2/22/medline PY - 2007/1/26/entrez SP - 893 EP - 900 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 27 IS - 4 N2 - The molecules that mediate neuron death in Alzheimer's disease (AD) are largely unknown. We report that beta-amyloid (Abeta), 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 Abeta-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 Abeta-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 Abeta and of dysregulated cell cycle proteins in AD and identify both Bim and cell cycle elements as potential therapeutic targets. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/17251431/Bim_is_elevated_in_Alzheimer's_disease_neurons_and_is_required_for_beta_amyloid_induced_neuronal_apoptosis_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=17251431 DB - PRIME DP - Unbound Medicine ER -