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Apoptosis in the nervous system

Nature volume 407, pages 802–809 (2000)Cite this article

Abstract

Neuronal apoptosis sculpts the developing brain and has a potentially important role in neurodegenerative diseases. The principal molecular components of the apoptosis programme in neurons include Apaf-1 (apoptotic protease-activating factor 1) and proteins of the Bcl-2 and caspase families. Neurotrophins regulate neuronal apoptosis through the action of critical protein kinase cascades, such as the phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase pathways. Similar cell-death-signalling pathways might be activated in neurodegenerative diseases by abnormal protein structures, such as amyloid fibrils in Alzheimer's disease. Elucidation of the cell death machinery in neurons promises to provide multiple points of therapeutic intervention in neurodegenerative diseases.

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Figure 1: Activation of apoptosis in sympathetic neurons by trophic factor withdrawal.
Figure 2: Neuronal survival pathways induced by the binding of NGF to its receptor TrkA.
Figure 3: Abnormal protein structures and the pathogenesis of neurodegenerative disease.
Figure 4: Cellular pathways of amyloid-β protein neurotoxicity in Alzheimer's disease.
Figure 5: SOD-1 mutations activate cell death pathways in familial amyotrophic lateral sclerosis.

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Acknowledgements

We thank M. Greenberg, M. Moskowitz, M. Deshmukh and E. Johnson for critical readings of the manuscript. This work was supported by grants from the NIH (to B.Y. and J.Y), a grant from the American Heart Association (to J.Y.), a Zenith Award from the Alzheimer's Association (to B.Y.) and a NIH MRRC core grant.

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  1. Department of Neurology Harvard Medical School and Division of Neuroscience, Children's Hospital, Enders 260, 300 Longwood Avenue, Boston, 02115, Massachusetts , USA

    Junying Yuan

  2. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Bruce A. Yankner

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Yuan, J., Yankner, B. Apoptosis in the nervous system. Nature 407, 802–809 (2000). https://doi.org/10.1038/35037739

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