Amyloid-β with isomerized Asp7 cytotoxicity is coupled to protein phosphorylation

Scientific Reports
O G ZatsepinaA A Makarov

Abstract

Neuronal dysfunction and loss associated with the accumulation of amyloid-β (Aβ) in the form of extracellular amyloid plaques and hyperphosphorylated tau in the form of intraneuronal neurofibrillary tangles represent key features of Alzheimer's disease (AD). Amyloid plaques found in the brains of AD patients are predominantly composed of Aβ42 and its multiple chemically or structurally modified isoforms. Recently, we demonstrated that Aβ42 with isomerised Asp7 (isoAβ42) which is one of the most abundant Aβ isoform in plaques, exhibited high neurotoxicity in human neuronal cells. Here, we show that, in SH-SY5Y neuroblastoma cells, the administration of synthetic isoAβ42 rather than intact Aβ42 resulted in a significantly higher level of protein phosphorylation, especially the phosphorylation of tau, tubulins, and matrin 3. IsoAβ42 induced a drastic reduction of tau protein levels. Our data demonstrate, for the first time, that isoAβ42, being to date the only known synthetic Aβ species to cause AD-like amyloidogenesis in an animal AD model, induced cell death by disabling structural proteins in a manner characteristic of that observed in the neurons of AD patients. The data emphasize an important role of isoAβ42 in AD progression...Continue Reading

References

May 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·M D WeingartenM W Kirschner
Oct 1, 1992·Molecular Biology of the Cell·D N DrechselM W Kirschner
Nov 1, 1985·Archives of Neurology·Z S Khachaturian
Jan 1, 1994·European Journal of Immunology·S C LeyM J Crumpton
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A E RoherM J Ball
Nov 24, 1998·Journal of Neuropathology and Experimental Neurology·R HosodaT Iwatsubo
Apr 3, 2003·Neuron·Flavio KamenetzRoberto Malinow
Jul 2, 2004·The New England Journal of Medicine·Jeffrey L Cummings
Oct 14, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sylvain Lesné, Linda Kotilinek
Sep 23, 2006·Science·Melanie Meyer-LuehmannMathias Jucker
Feb 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Robert M KoffieTara L Spires-Jones
May 22, 2009·Journal of Neurochemistry·John Hardy
Nov 11, 2010·Naunyn-Schmiedeberg's Archives of Pharmacology·Ying PengXiaoliang Wang
May 11, 2011·Neuron·Meaghan MorrisLennart Mucke
May 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Samuel I A CohenTuomas P J Knowles
Apr 22, 2014·Journal of Internal Medicine·J HardyH Zetterberg
Aug 20, 2014·Neurobiology of Disease·Rodrigo A QuintanillaGail V W Johnson
Jul 15, 2015·Structure·Martin SchwalbeMarkus Zweckstetter
Mar 8, 2016·Biochimica Et Biophysica Acta·Yulia V LyupinaVictor S Mikhailov
Mar 31, 2016·EMBO Molecular Medicine·Dennis J Selkoe, John Hardy
Jul 29, 2016·Scientific Reports·Ana Gabriela HenriquesOdete A B da Cruz E Silva
May 31, 2017·Frontiers in Genetics·Evgeny P BarykinAlexander A Makarov

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
FCS

Software Mentioned

Fiji ImageJ
Mascot
Image Lab

Related Concepts

Related Feeds

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.

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: 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.