Trafficking and proteolytic processing of APP.

Cold Spring Harbor Perspectives in Medicine
Christian HaassSangram Sisodia

Abstract

Accumulations of insoluble deposits of amyloid β-peptide are major pathological hallmarks of Alzheimer disease. Amyloid β-peptide is derived by sequential proteolytic processing from a large type I trans-membrane protein, the β-amyloid precursor protein. The proteolytic enzymes involved in its processing are named secretases. β- and γ-secretase liberate by sequential cleavage the neurotoxic amyloid β-peptide, whereas α-secretase prevents its generation by cleaving within the middle of the amyloid domain. In this chapter we describe the cell biological and biochemical characteristics of the three secretase activities involved in the proteolytic processing of the precursor protein. In addition we outline how the precursor protein maturates and traffics through the secretory pathway to reach the subcellular locations where the individual secretases are preferentially active. Furthermore, we illuminate how neuronal activity and mutations which cause familial Alzheimer disease affect amyloid β-peptide generation and therefore disease onset and progression.

References

Jul 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S S Sisodia
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·E H KooD L Price
Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J D BuxbaumP Greengard
Feb 24, 1995·The Journal of Biological Chemistry·A LaiI S Trowbridge
Jan 1, 1994·Acta Neuropathologica·I R Mackenzie, L A Miller
Feb 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·C HaassD J Selkoe
Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J BusciglioB A Yankner
Jun 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·R M NitschR J Wurtman
Mar 1, 1997·Annals of Neurology·G K GourasS Gandy
Sep 11, 1999·Trends in Neurosciences·W Annaert, B De Strooper
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·X LinJ Tang
Apr 6, 2000·The Journal of Biological Chemistry·B D BennettR Vassar
May 10, 2000·The Journal of Biological Chemistry·A CapellC Haass

❮ Previous
Next ❯

Citations

Jul 3, 2013·Cellular and Molecular Neurobiology·Soheila SaberiClaire Goldsbury
Sep 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yuan TianPaul Greengard
Jun 8, 2012·Cold Spring Harbor Perspectives in Medicine·Colin L Masters, Dennis J Selkoe
Feb 23, 2012·Cold Spring Harbor Perspectives in Medicine·Ulrike C Müller, Hui Zheng
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·Bart De StrooperMichael S Wolfe
Mar 7, 2012·Cold Spring Harbor Perspectives in Medicine·David M HoltzmanGuojun Bu
Jul 5, 2012·Cold Spring Harbor Perspectives in Medicine·Lennart Mucke, Dennis J Selkoe
Jun 8, 2012·Cold Spring Harbor Perspectives in Medicine·Takaomi Saido, Malcolm A Leissring
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·Dennis SelkoeDavid Holtzman
Jan 15, 2014·Molecular Neurodegeneration·Shangtong JiangYun-wu Zhang
Jul 5, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Raja BhattacharyyaDora M Kovacs
Jan 8, 2014·Annual Review of Pharmacology and Toxicology·Karen Chiang, Edward H Koo
Dec 7, 2013·International Journal of Cell Biology·Gunnar K Gouras
Sep 14, 2013·Brain : a Journal of Neurology·Jose V Sanchez-MutManel Esteller
Feb 15, 2014·Human Molecular Genetics·Christina R MuratoreTracy L Young-Pearse
Feb 21, 2014·Molecular Neurobiology·Xiaoguang YangJames C-M Lee
Nov 14, 2014·Molecular Biology of the Cell·Emily D NiederstLawrence S B Goldstein
Sep 5, 2013·Molecular and Cellular Biology·Tilman BurgertThomas E Willnow
Jan 2, 2016·Journal of Proteomics·Pascal SteffenHartmut Schlüter
Apr 23, 2013·Expert Opinion on Therapeutic Targets·Mari TakaloMikko Hiltunen
Nov 4, 2015·Journal of Neurotrauma·Shuzhen GuoEng H Lo
Feb 10, 2016·Frontiers in Neuroscience·Katja KühbachOliver Bannach
Dec 3, 2014·Neuroscience and Biobehavioral Reviews·Weihong Pan, Abba J Kastin
Feb 4, 2016·Trends in Pharmacological Sciences·Carole DeytsAngèle T Parent
Dec 22, 2014·Journal of Molecular Biology·Sandra HoefgenManuel E Than
Feb 26, 2016·Neuroscience Research·Saket Milind NigamLennart Brodin
Mar 19, 2013·Experimental Cell Research·Masanori Nakayama, Philipp Berger
Feb 20, 2013·Molecular Genetics and Metabolism·Friedrich P Thinnes
Sep 26, 2015·Traffic·Margaret S Robinson
Dec 23, 2015·International Journal of Molecular Sciences·Ebbe Toftgaard PoulsenCarmela Matrone
Dec 4, 2015·Membranes·Matthew A BarrettMaikel C Rheinstädter
Feb 18, 2016·Neural Plasticity·Bianca SeifertTanja Brigadski
Sep 6, 2015·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Ellen HubinKris Pauwels

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.