Mol Neurobiol DOI 10.1007/s12035-014-8652-6
Cellular Membrane Fluidity in Amyloid Precursor Protein Processing Xiaoguang Yang & Grace Y. Sun & Gunter P. Eckert & James C-M. Lee
Received: 22 October 2013 / Accepted: 23 January 2014 # Springer Science+Business Media New York 2014
Abstract The senile plaque is a pathologic hallmark of Alzheimer's disease (AD). Amyloid-β peptide (Aβ), the main constituent of senile plaques, is neurotoxic especially in its oligomeric form. Aβ is derived from the sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases in the amyloidogenic pathway. Alternatively, APP can be cleaved by α-secretases within the Aβ domain to produce neurotrophic and neuroprotective α-secretase-cleaved soluble APP (sAPPα) in the nonamyloidogenic pathway. Since APP and α-, β-, and γ-secretases are membrane proteins, APP processing should be highly dependent on the membrane composition and the biophysical properties of cellular membrane. In this review, we discuss the role of the biophysical properties of cellular membrane in APP processing, especially the effects of phospholipases A2 (PLA2s), fatty acids, cholesterol, and Aβ on membrane fluidity in relation to their effects on APP processing. X. Yang Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden G. Y. Sun Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA G. Y. Sun Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65211, USA G. P. Eckert (*) Department of Pharmacology, Goethe University, 60438 Frankfurt, Germany e-mail: [email protected] J. C.
Cellular Membrane Fluidity in Amyloid Precursor Protein Processing Xiaoguang Yang & Grace Y. Sun & Gunter P. Eckert & James C-M. Lee
Received: 22 October 2013 / Accepted: 23 January 2014 # Springer Science+Business Media New York 2014
Abstract The senile plaque is a pathologic hallmark of Alzheimer's disease (AD). Amyloid-β peptide (Aβ), the main constituent of senile plaques, is neurotoxic especially in its oligomeric form. Aβ is derived from the sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases in the amyloidogenic pathway. Alternatively, APP can be cleaved by α-secretases within the Aβ domain to produce neurotrophic and neuroprotective α-secretase-cleaved soluble APP (sAPPα) in the nonamyloidogenic pathway. Since APP and α-, β-, and γ-secretases are membrane proteins, APP processing should be highly dependent on the membrane composition and the biophysical properties of cellular membrane. In this review, we discuss the role of the biophysical properties of cellular membrane in APP processing, especially the effects of phospholipases A2 (PLA2s), fatty acids, cholesterol, and Aβ on membrane fluidity in relation to their effects on APP processing. X. Yang Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden G. Y. Sun Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA G. Y. Sun Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65211, USA G. P. Eckert (*) Department of Pharmacology, Goethe University, 60438 Frankfurt, Germany e-mail: [email protected] J. C.
