An RNA aptamer with potent affinity for a toxic dimer of amyloid β42 has potential utility for histochemical studies of Alzheimer's disease.

The Journal of Biological Chemistry
Kazuma MurakamiKazuhiro Irie

Abstract

Oligomers of β-amyloid 42 (Aβ42), rather than fibrils, drive the pathogenesis of Alzheimer's disease (AD). In particular, toxic oligomeric species called protofibrils (PFs) have attracted significant attention. Herein, we report RNA aptamers with higher affinity toward PFs derived from a toxic Aβ42 dimer than toward fibrils produced from WT Aβ42 or from a toxic, conformationally constrained Aβ42 variant, E22P-Aβ42. We obtained these RNA aptamers by using the preincubated dimer model of E22P-Aβ42, which dimerized via a linker located at Val-40, as the target of in vitro selection. This dimer formed PFs during incubation. Several physicochemical characteristics of an identified aptamer, E22P-AbD43, suggested that preferential affinity of this aptamer toward PFs is due to its higher affinity for the toxic dimer unit (KD = 20 ± 6.0 nm) of Aβ42 than for less-toxic Aβ40 aggregates. Comparison of CD data from the full-length and random regions of E22P-AbD43 suggested that the preferential binding of E22P-AbD43 toward the dimer might be related to the formation of a G-quadruplex structure. E22P-AbD43 significantly inhibited the nucleation phase of the dimer and its associated neurotoxicity in SH-SY5Y human neuroblastoma cells. Of note,...Continue Reading

References

Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
May 16, 1984·Biochemical and Biophysical Research Communications·G G Glenner, C W Wong
Feb 1, 1997·Chemistry & Biology·J D HarperP T Lansbury
Aug 29, 1997·The Journal of Biological Chemistry·D M WalshD B Teplow
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M P LambertW L Klein
Nov 26, 1998·Acta Neuropathologica·S D GinsbergJ Q Trojanowski
Apr 10, 1999·Methods : a Companion to Methods in Enzymology·J M Lahti
Oct 3, 1999·Methods in Enzymology·H Naiki, F Gejyo
Feb 1, 2002·Biochemical and Biophysical Research Communications·Francisco YleraJens Peter Fürste
May 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Minako HoshiKazuki Sato
Oct 2, 2004·The Journal of Biological Chemistry·Akira MorimotoTakuji Shirasawa
Nov 9, 2004·Biochemical and Biophysical Research Communications·Yuko HorikoshiHaruyasu Yamaguchi
Oct 3, 2006·Nucleic Acids Research·Sarah BurgeStephen Neidle
Jan 25, 2007·Nature Reviews. Molecular Cell Biology·Christian Haass, Dennis J Selkoe
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Sep 26, 2008·The Journal of Biological Chemistry·Kenjiro OnoDavid B Teplow
Oct 11, 2008·The Journal of Biological Chemistry·Robin RoychaudhuriDavid B Teplow
Dec 31, 2008·Chembiochem : a European Journal of Chemical Biology·Yuichi MasudaKazuhiro Irie
Feb 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Robert M KoffieTara L Spires-Jones
May 14, 2009·Nucleic Acids Research·Kengo SatoToutai Mituyama
Aug 12, 2009·Molecular BioSystems·Tsuyoshi TakahashiHisakazu Mihara
Mar 5, 2011·Nature Protocols·Ana M Rossi, Colin W Taylor
Aug 10, 2011·Journal of the American Chemical Society·Valery AndrushchenkoPetr Bour
Jun 16, 2012·Analytical Chemistry·Kaori TsukakoshiKazunori Ikebukuro
Nov 17, 2010·ACS Chemical Neuroscience·Kazuma MurakamiKazuhiro Irie
Mar 4, 2014·PloS One·Christian T FarrarBradley T Hyman
Jan 1, 2016·Bioorganic & Medicinal Chemistry·Mizuho HanakiKazuhiro Irie
May 11, 2016·Proceedings of the National Academy of Sciences of the United States of America·Takahiro Watanabe-NakayamaMasahito Yamada
Oct 19, 2016·Chemical Communications : Chem Comm·Kaori TsukakoshiKazunori Ikebukuro
Nov 4, 2016·Nature Reviews. Drug Discovery·Jiehua Zhou, John Rossi
Dec 28, 2016·ACS Chemical Neuroscience·Yumi IrieKazuhiro Irie
Apr 20, 2018·Chemical Communications : Chem Comm·Madhuri ChakravarthyRakesh N Veedu

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

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.