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Roles of amyloid precursor protein family members in neuroprotection, stress signaling and aging

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Abstract

The roles of amyloid precursor protein (APP) family members in normal brain function are poorly understood. Under physiological conditions the majority of APP appears to be processed along the non-amyloidogenic pathway leading to the formation of the secreted N-terminal APP fragment sAPPα. This cleavage product of APP has been implicated in several physiological processes such as neuroprotection, synaptic plasticity, neurite outgrowth and synaptogenesis. In this review we focus on the role of APP family members in neuroprotection and summarize the cellular and molecular mechanisms which are believed to mediate this effect. We propose that a reduction of APP processing along the non-amyloidogenic pathway during brain aging could result in an enhanced susceptibility of neurons to cellular stress and could contribute to neurodegeneration in Alzheimer’s disease.

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Acknowledgments

The authors thank all coworkers who have been involved in the studies that have provided the basis for this review. This study was supported by the DFG (KO 1998/6-1, BE 1475/8-1, DE 551/11-1).

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  1. Experimental Neurosurgery, Neuroscience Center, Goethe University Hospital, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany

    Donat Kögel

  2. Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany

    Thomas Deller

  3. Institute for Pathobiochemistry, University Medical Center, Johannes-Gutenberg-University, Duesbergweg 6, 55099, Mainz, Germany

    Christian Behl

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  1. Donat Kögel
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Correspondence to Donat Kögel.

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Kögel, D., Deller, T. & Behl, C. Roles of amyloid precursor protein family members in neuroprotection, stress signaling and aging. Exp Brain Res 217, 471–479 (2012). https://doi.org/10.1007/s00221-011-2932-4

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