Tauopathy-Associated Tau Fragment Ending at Amino Acid 224 Is Generated by Calpain-2 Cleavage.

Journal of Alzheimer's Disease : JAD
Claudia CicognolaKina Höglund

Abstract

Tau aggregation in neurons and glial cells characterizes tauopathies as Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Tau proteolysis has been proposed as a trigger for tau aggregation and tau fragments have been observed in brain and cerebrospinal fluid (CSF). Our group identified a major tau cleavage at amino acid (aa) 224 in CSF; N-terminal tau fragments ending at aa 224 (N-224) were significantly increased in AD and lacked correlation to total tau (t-tau) and phosphorylated tau (p-tau) in PSP and CBD. Previous studies have shown cleavage from calpain proteases at sites adjacent to aa 224. Our aim was to investigate if calpain-1 or -2 could be responsible for cleavage at aa 224. Proteolytic activity of calpain-1, calpain-2, and brain protein extract was assessed on a custom tau peptide (aa 220-228), engineered with fluorescence resonance energy transfer (FRET) technology. Findings were confirmed with in-gel trypsination and mass spectrometry (MS) analysis of brain-derived bands with proteolytic activity on the FRET substrate. Finally, knock-down of the calpain-2 catalytic subunit gene (CAPN2) was performed in a neuroblastoma cell line (SH-SY5Y). Calpain-2 and brain protei...Continue Reading

References

Jan 1, 1991·Acta Neuropathologica·H Braak, E Braak
Oct 1, 1995·European Journal of Biochemistry·L S Yang, H Ksiezak-Reding
Sep 15, 1996·The Biochemical Journal·A BakiP Friedrich
Dec 4, 1996·Biochemical and Biophysical Research Communications·E MelloniS Pontremoli
Apr 25, 1997·The Journal of Biological Chemistry·J S ElceJ S Arthur
Mar 15, 2002·Cell·Tudor MoldoveanuPeter L Davies
Jul 5, 2003·Physiological Reviews·Darrell E GollJinyang Cong
Jul 31, 2003·Proceedings of the National Academy of Sciences of the United States of America·T Chris GamblinVincent L Cryns
Jun 3, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·So-Young Park, Adriana Ferreira
Jul 22, 2006·The Journal of Physiology·Robyn M MurphyGraham D Lamb
Nov 23, 2006·Biochimica Et Biophysica Acta·Yi WenJames W Simpkins
May 31, 2007·Proceedings of the National Academy of Sciences of the United States of America·Y P WangE-M Mandelkow
Aug 22, 2007·Neurobiology of Aging·B BorroniM Di Luca
Mar 21, 2008·Journal of Proteome Research·Erik PorteliusJohan Gobom
Aug 8, 2008·Molecular Neurobiology·P S VoslerJ Chen
Sep 13, 2013·Frontiers in Neurology·Adrianne S ChesserGail V W Johnson
Oct 12, 2013·PloS One·Jere E MeredithCharles F Albright
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Konstantin I PiatkovAlexander Varshavsky
Jul 11, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mala V RaoRalph A Nixon
Feb 15, 2016·Trends in Neurosciences·Michel Baudry, Xiaoning Bi
Apr 3, 2016·Acta Neuropathologica Communications·Ksenia KurbatskayaWendy Noble
Oct 26, 2016·Brain Research Bulletin·Thomas ArendtMax Holzer
Dec 19, 2016·Bioorganic & Medicinal Chemistry Letters·Priya SandhuAjoy Basak
Jan 4, 2017·Proteomics·Karl T HanssonJohan Gobom
Mar 24, 2018·Neuron·Chihiro SatoRandall J Bateman
Apr 10, 2018·Journal of Alzheimer's Disease : JAD·James P QuinnNigel M Hooper
Nov 13, 2018·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Zhicheng ChenDominic M Walsh

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
FRET
transfection
PCR
electrophoresis
gene knock-down

Software Mentioned

SDS
Proteome Discoverer
Image J Fiji
Mascot search engine

Related Concepts

Related Feeds

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.

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.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.