Oleuropein aglycone stabilizes the monomeric α-synuclein and favours the growth of non-toxic aggregates

Scientific Reports
Luana PalazziPatrizia Polverino de Laureto

Abstract

α-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD); its deposits are found as amyloid fibrils in Lewy bodies and Lewy neurites, the histopathological hallmarks of PD. Amyloid fibrillation is a progressive polymerization path starting from peptide/protein misfolding and proceeding through the transient growth of oligomeric intermediates widely considered as the most toxic species. Consequently, a promising approach of intervention against PD might be preventing α-synuclein build-up, misfolding and aggregation. A possible strategy involves the use of small molecules able to slow down the aggregation process or to alter oligomer conformation favouring the growth of non-pathogenic species. Here, we show that oleuropein aglycone (OleA), the main olive oil polyphenol, exhibits anti-amyloidogenic power in vitro by interacting with, and stabilizing, α-synuclein monomers thus hampering the growth of on-pathway oligomers and favouring the growth of stable and harmless aggregates with no tendency to evolve into other cytotoxic amyloids. We investigated the molecular basis of such interference by both biophysical techniques and limited proteolysis; aggregate morphology was monitored by electron microscopy. We also...Continue Reading

References

Nov 1, 1989·Analytical Biochemistry·S C Gill, P H von Hippel
Aug 15, 1974·European Journal of Biochemistry·W EbelingH Lang
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K UédaT Saitoh
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M G SpillantiniM Goedert
Oct 30, 1998·Molecular Medicine Today·O RiessR Krüger
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·J E GalvinJ Q Trojanowski
Jan 22, 2001·The Journal of Biological Chemistry·V N UverskyA L Fink
Apr 5, 2001·Journal of Molecular Biology·D EliezerG Browne
Feb 15, 2003·The Journal of Biological Chemistry·Sreeganga ChandraThomas C Südhof
Nov 1, 2003·Science·A B SingletonK Gwinn-Hardy
Nov 5, 2003·Journal of Molecular Biology·Patrizia Polverino de LauretoAngelo Fontana
Apr 21, 2004·The Journal of Biological Chemistry·Min ZhuAnthony L Fink
Jan 13, 2005·Journal of the American Chemical Society·Matthew M DedmonChristopher M Dobson
May 10, 2006·Biochemistry·Masami MasudaMasato Hasegawa
Jul 25, 2006·Journal of Molecular Biology·Erica FrareAngelo Fontana
Jan 4, 2008·Pharmaceutical Research·Andrea HaweWim Jiskoot
May 31, 2008·Nature Structural & Molecular Biology·Dagmar E EhrnhoeferErich E Wanker
Sep 9, 2008·Journal of Molecular Biology·Dong-Pyo HongVladimir N Uversky
Nov 4, 2008·Molecular Neurodegeneration·Jada LewisMatthew J Farrer
Dec 2, 2008·Trends in Pharmacological Sciences·Anthony H V Schapira
Jul 21, 2009·The Journal of Nutritional Biochemistry·Stefania RigacciAndrea Berti
Aug 4, 2009·FEBS Letters·Masaki Wakabayashi, Katsumi Matsuzaki
Aug 19, 2009·Journal of Neurochemistry·Karin M DanzerBastian Hengerer
Sep 15, 2009·Journal of Molecular Biology·Giorgia De FranceschiPatrizia Polverino de Laureto
Apr 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jan BieschkeErich E Wanker
Aug 28, 2010·Science·Jacqueline BurréThomas C Südhof
Dec 3, 2010·Journal of Agricultural and Food Chemistry·Francisca Gutierrez-RosalesMaría Isabel Mínguez-Mosquera
Dec 24, 2010·Scientia pharmaceutica·Syed Haris Omar
Feb 22, 2011·Neurochemistry International·Anthony DaccachePhilippe Cotelle
Aug 30, 2012·Journal of Biophotonics·Daniele NosiFranco Quercioli
Dec 21, 2012·Nature Reviews. Neuroscience·Hilal A LashuelEliezer Masliah
Mar 21, 2013·ACS Chemical Neuroscience·Pradeep K SinghSamir K Maji
May 16, 2013·Movement Disorders : Official Journal of the Movement Disorder Society·Christos ProukakisAnthony H Schapira
Jun 15, 2013·Nature·Jacqueline BurréThomas C Südhof
Sep 10, 2013·Biophysical Journal·Santiago Esteban-MartínXavier Salvatella
Mar 26, 2014·Brain : a Journal of Neurology·Edward RockensteinEliezer Masliah

❮ Previous
Next ❯

Citations

Jan 19, 2019·The Journal of Biological Chemistry·Hossein Mohammad-BeigiDaniel E Otzen
May 30, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ana Karković MarkovićCvijeta Jakobušić Brala
Sep 6, 2019·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Nazareno GonzálezClaudio O Fernández
Oct 6, 2019·Acta Pharmacologica Sinica·Ming-Ming XuGeorge D Mellick
Feb 12, 2020·Journal of Biomolecular Structure & Dynamics·Priyanka BorahVenkata Satish Kumar Mattaparthi
Sep 27, 2018·International Journal of Molecular Sciences·Ganapathy SivakumarLuigi Gentile
Jul 28, 2020·International Journal of Molecular Sciences·Oscar Palomino-HernandezClaudio O Fernandez
Aug 14, 2020·Pharmaceuticals·Marzia VasarriDonatella Degl'Innocenti
Apr 12, 2020·International Journal of Molecular Sciences·Giovanni BrunettiNadine Saul
Jul 22, 2018·Cellular and Molecular Life Sciences : CMLS·Zohra DhouafliInes Moreno-Gonzalez
Aug 14, 2019·International Journal of Molecular Sciences·Elise LévyLaurence Vernis
Jul 8, 2020·Antioxidants·Han-A Park, Amy C Ellis
Sep 13, 2018·International Journal of Molecular Sciences·Sofia GiorgettiFrancesco Antonio Aprile
Jan 16, 2020·Antioxidants·Rui F M Silva, Lea Pogačnik
Aug 2, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Manuela LeriDonatella Degl'Innocenti
Jul 3, 2021·International Journal of Molecular Sciences·Luana PalazziPatrizia Polverino de Laureto
Nov 6, 2021·Frontiers in Chemistry·Paola CostanzoAntonio Procopio
Nov 14, 2021·Comprehensive Reviews in Food Science and Food Safety·Joana MadureiraLillian Barros

❮ Previous
Next ❯

Methods Mentioned

BETA
Gel filtration
NMR
Assay
transmission
dynamic light scattering
FRET

Software Mentioned

ImageJ

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2022 Meta ULC. All rights reserved