Nitration of hIAPP promotes its toxic oligomer formation and exacerbates its toxicity towards INS-1 cells

Nitric Oxide ◽  
2019 ◽  
Vol 87 ◽  
pp. 23-30 ◽  
Author(s):  
Jie Zhao ◽  
Jinming Wu ◽  
Zhen Yang ◽  
Lei Ouyang ◽  
Lihua Zhu ◽  
...  
Keyword(s):  
Oligomer Formation ◽  
Toxic Oligomer

scholarly journals Biocompatible and blood–brain barrier permeable carbon dots for inhibition of Aβ fibrillation and toxicity, and BACE1 activity

Nanoscale ◽  
2017 ◽  
Vol 9 (35) ◽  
pp. 12862-12866 ◽  
Author(s):  
Xu Han ◽  
Zhifeng Jing ◽  
Wei Wu ◽  
Bing Zou ◽  
Zhili Peng ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Carbon Dots ◽  
Brain Barrier ◽  
Oligomer Formation ◽  
Blood Brain ◽  
Bace1 Activity ◽  
Toxic Oligomer

The blood–brain barrier permeable C-Dots can deactivate the BACE1 and further inhibit Aβ fibrillation and toxic oligomer formation.

scholarly journals DJ-1 Acts as a Scavenger of α-Synuclein Oligomers and Restores Monomeric Glycated α-Synuclein

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1466
Author(s):  
Tamr B. Atieh ◽  
Jonathan Roth ◽  
Xue Yang ◽  
Cody L. Hoop ◽  
Jean Baum
Keyword(s):  
Critical Role ◽  
Force Microscopy ◽  
Oligomer Formation ◽  
Atomic Force ◽  
Glycation End Products ◽  
Catalytic Cysteine ◽  
Solution Nuclear Magnetic Resonance ◽  
Integrate Solution ◽  
Toxic Oligomer

Glycation of α-synuclein (αSyn), as occurs with aging, has been linked to the progression of Parkinson’s disease (PD) through the promotion of advanced glycation end-products and the formation of toxic oligomers that cannot be properly cleared from neurons. DJ-1, an antioxidative protein that plays a critical role in PD pathology, has been proposed to repair glycation in proteins, yet a mechanism has not been elucidated. In this study, we integrate solution nuclear magnetic resonance (NMR) spectroscopy and liquid atomic force microscopy (AFM) techniques to characterize glycated N-terminally acetylated-αSyn (glyc-ac-αSyn) and its interaction with DJ-1. Glycation of ac-αSyn by methylglyoxal increases oligomer formation, as visualized by AFM in solution, resulting in decreased dynamics of the monomer amide backbone around the Lys residues, as measured using NMR. Upon addition of DJ-1, this NMR signature of glyc-ac-αSyn monomers reverts to a native ac-αSyn-like character. This phenomenon is reversible upon removal of DJ-1 from the solution. Using relaxation-based NMR, we have identified the binding site on DJ-1 for glycated and native ac-αSyn as the catalytic pocket and established that the oxidation state of the catalytic cysteine is imperative for binding. Based on our results, we propose a novel mechanism by which DJ-1 scavenges glyc-ac-αSyn oligomers without chemical deglycation, suppresses glyc-ac-αSyn monomer–oligomer interactions, and releases free glyc-ac-αSyn monomers in solution. The interference of DJ-1 with ac-αSyn oligomers may promote free ac-αSyn monomer in solution and suppress the propagation of toxic oligomer and fibril species. These results expand the understanding of the role of DJ-1 in PD pathology by acting as a scavenger for aggregated αSyn.

Inhibition of human IAPP fibril formation does not prevent β-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP

2006 ◽  
Vol 291 (6) ◽  
pp. E1317-E1324 ◽  
Author(s):  
Juris J. Meier ◽  
Rakez Kayed ◽  
Chia-Yu Lin ◽  
Tatyana Gurlo ◽  
Leena Haataja ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Screening Tools ◽  
Β Cells ◽  
Β Cell ◽  
Islet Amyloid ◽  
Oligomer Formation ◽  
Amyloid Fibril Formation ◽  
Toxic Oligomer

Type 2 diabetes mellitus (T2DM) is characterized by an ∼60% deficit in β-cell mass, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). Human IAPP (hIAPP) forms oligomers, leading to either amyloid fibrils or toxic oligomers in an aqueous solution in vitro. Either application of hIAPP on or overexpression of hIAPP in cells induces apoptosis. It remains controversial whether the fibrils or smaller toxic oligomers induce β-cell apoptosis. Rifampicin prevents hIAPP amyloid fibril formation and has been proposed as a potential target for prevention of T2DM. We examined the actions of rifampicin on hIAPP amyloid fibril and toxic oligomer formation as well as its ability to protect β-cells from either application of hIAPP or endogenous overexpression of hIAPP (transgenic rats and adenovirus-transduced β-cells). We report that rifampicin (Acocella G. Clin Pharmacokinet 3: 108–127, 1978) prevents hIAPP fibril formation, but not formation of toxic hIAPP oligomers (Bates G. Lancet 361: 1642–1644, 2003), and does not protect β-cells from apoptosis induced by either overexpression or application of hIAPP. These data emphasize that toxic hIAPP oligomers, rather than hIAPP fibrils, initiate β-cell apoptosis and that screening tools to identify inhibitors of amyloid fibril formation are likely to be less useful than those that identify inhibitors of toxic oligomer formation. Finally, rifampicin and related molecules do not appear to be useful as candidates for prevention of T2DM.

Review on the Application of Mixed-mode Chromatography for Separation of Structure Isoforms

2018 ◽  
Vol 20 (1) ◽  
pp. 56-60 ◽  
Author(s):  
Tsutomu Arakawa
Keyword(s):  
Ion Exchange ◽  
Mixed Mode ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Charged State ◽  
Partial Structure ◽  
Reverse Phase ◽  
Oligomer Formation ◽  
Structure Rearrangement ◽  
Disulfide Scrambling

Proteins often generate structure isoforms naturally or artificially due to, for example, different glycosylation, disulfide scrambling, partial structure rearrangement, oligomer formation or chemical modification. The isoform formations are normally accompanied by alterations in charged state or hydrophobicity. Thus, isoforms can be fractionated by reverse-phase, hydrophobic interaction or ion exchange chromatography. We have applied mixed-mode chromatography for fractionation of isoforms for several model proteins and observed that cation exchange Capto MMC and anion exchange Capto adhere columns are effective in separating conformational isoforms and self-associated oligomers.

scholarly journals Hsp70 chaperone blocks α-synuclein oligomer formation via a novel engagement mechanism

2021 ◽  
Vol 296 ◽  
pp. 100613
Author(s):  
Jiahui Tao ◽  
Amandine Berthet ◽  
Y. Rose Citron ◽  
Paraskevi L. Tsiolaki ◽  
Robert Stanley ◽  
...  
Keyword(s):  
Oligomer Formation ◽  
Hsp70 Chaperone

scholarly journals Conditions of the Oligomer Formation of VTES and VTMS Suitable for the Donation of Effective Hydrophobicity to TiO2.

2002 ◽  
Vol 53 (4) ◽  
pp. 273-277 ◽  
Author(s):  
Sumiko SANUKI ◽  
Yoshihiko NISHI ◽  
Toshihiro YOSHIMOTO ◽  
Hiroshi MAJIMA
Keyword(s):  
Oligomer Formation

Dynamics of oligomer formation by denatured carbonic anhydrase II

2008 ◽  
Vol 1784 (5) ◽  
pp. 834-842 ◽  
Author(s):  
Dmitry A. Prokhorov ◽  
Alexander A. Timchenko ◽  
Vladimir N. Uversky ◽  
Vladimir S. Khristoforov ◽  
Hiroshi Kihara ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
Oligomer Formation
Sign in / Sign up

Export Citation Format

Share Document