Alzheimer-associated cerebrospinal fluid fragments of neurogranin are generated by Calpain-1 and prolyl endopeptidase

Molecular Neurodegeneration
Bruno BeckerKaj Blennow

Abstract

Neurogranin (Ng) is a small 7.6 kDa postsynaptic protein that has been detected at elevated concentrations in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), both as a full-length molecule and as fragments from its C-terminal half. Ng is involved in postsynaptic calcium (Ca) signal transduction and memory formation via binding to calmodulin in a Ca-dependent manner. The mechanism of Ng secretion from neurons to CSF is currently unknown, but enzymatic cleavage of Ng may be of relevance. Therefore, the aim of the study was to identify the enzymes responsible for the cleavage of Ng, yielding the Ng fragment pattern of C-terminal fragments detectable and increased in CSF of AD patients. Fluorigenic quenched FRET probes containing sequences of Ng were utilized to identify Ng cleaving activities among enzymes known to have increased activity in AD and in chromatographically fractionated mouse brain extracts. Human Calpain-1 and prolyl endopeptidase were identified as the candidate enzymes involved in the formation of endogenous Ng peptides present in CSF, cleaving mainly in the central region of Ng, and between amino acids 75_76 in the Ng sequence, respectively. The cleavage by Calpain-1 affects the IQ domain of ...Continue Reading

References

May 15, 1991·The Biochemical Journal·S Kalwant, A G Porter
Dec 1, 1987·Biochemical Medicine and Metabolic Biology·M Hagihara, T Nagatsu
Apr 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K SaitoR A Nixon
Apr 1, 1997·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A R Rhoads, F Friedberg
Dec 13, 1997·Molecular Neurobiology·D D Gerendasy, J G Sutcliffe
Jun 18, 1998·International Psychogeriatrics·P Davidsson, K Blennow
Mar 13, 1999·The Journal of Biological Chemistry·L PrichardD R Storm
Feb 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·P W VanderklishG M Edelman
Oct 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·J H PakK P Huang
Mar 26, 2002·FEBS Letters·Martin Bähler, Allen Rhoads
Nov 26, 2002·European Journal of Biochemistry·Ingo SchulzHans-Ulrich Demuth
Sep 25, 2004·The Journal of Comparative Neurology·Ilyas SingecMichael Frotscher
Jul 6, 2005·Peptides·Inger BrandtAnne-Marie Lambeir
Nov 18, 2005·Neurobiology of Aging·Stephen W ScheffElliott J Mufson
May 9, 2006·Cell Biochemistry and Biophysics·Dean Rea, Vilmos Fülöp
Feb 14, 2007·The Biochemical Journal·Irene Domínguez-GonzálezF Javier Díez-Guerra
Apr 10, 2008·Science Signaling·Jing LiuKevin K W Wang
Jul 2, 2008·Annual Review of Cell and Developmental Biology·Walter Nickel, Matthias Seedorf
Aug 19, 2009·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Timo T MyöhänenPekka T Männistö
Aug 29, 2009·The EMBO Journal·Ling ZhongNashaat Z Gerges
Sep 16, 2009·The Biochemical Journal·Alberto Garrido-GarcíaF Javier Díez-Guerra
Nov 17, 2009·Biochemistry·Whitney M NolteAlan Saghatelian
Dec 24, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Hlin KvartsbergKaj Blennow
Sep 17, 2015·Brain : a Journal of Neurology·Erik PorteliusUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Jan 2, 2016·Experimental Neurology·Kanwardeep Kaleka, Nashaat Gerges
Jan 20, 2016·Annals of Clinical and Translational Neurology·Shorena JanelidzeOskar Hansson
Jan 31, 2016·Neurology·Henrietta WellingtonHenrik Zetterberg
Mar 22, 2016·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Corinna HöflingJ Arturo García-Horsman

❮ Previous
Next ❯

Citations

May 19, 2020·Aging·Mei XueUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Sep 12, 2020·Biomarker Insights·Elena CamporesiHenrik Zetterberg
Apr 26, 2019·Molecular Neurobiology·Alberto Garrido-GarcíaF Javier Díez-Guerra
Mar 8, 2020·Journal of Alzheimer's Disease : JAD·Claudia CicognolaKina Höglund
Nov 14, 2019·Neural Regeneration Research·Anna Villar-PiqueFranc Llorens
Oct 21, 2020·Biomedicines·Adrian Florian BălașaAlexandru Mihai Grumezescu
Nov 30, 2020·Journal of Neurochemistry·Faisal Hayat NazirBruno Becker
Nov 3, 2020·Frontiers in Aging Neuroscience·Yang XiangYongjian Yang
Mar 11, 2021·The International Journal of Neuroscience·Nina PesterevaMarina Karpenko
Jan 5, 2022·Neurochemical Research·Heena KhanKomal Thapa

❮ Previous
Next ❯

Datasets Mentioned

BETA
RC201209

Methods Mentioned

BETA
electrophoresis
FRET
size exclusion chromatography
ELISA
nuclear translocation

Software Mentioned

PEAKS Studio
Mascot Daemon
Mascot Distiller
Mascot engine
Mascot

Related Concepts

Related Feeds

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.