Amyloid-β Peptide Induces Prion Protein Amyloid Formation: Evidence for Its Widespread Amyloidogenic Effect

2018 ◽  
Vol 130 (21) ◽  
pp. 6194-6197 ◽  
Author(s):  
Ryo Honda
Keyword(s):  
Prion Protein ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Formation

Restored degradation of the Alzheimer’s amyloid-β peptide by targeting amyloid formation

2009 ◽  
Vol 108 (5) ◽  
pp. 1198-1207 ◽  
Author(s):  
Peter J. Crouch ◽  
Deborah J. Tew ◽  
Tai Du ◽  
Diem Ngoc Nguyen ◽  
Aphrodite Caragounis ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Formation

The Amyloid-β Peptide in Amyloid Formation Processes: Interactions with Blood Proteins and Naturally Occurring Metal Ions

2016 ◽  
Vol 57 (7-8) ◽  
pp. 674-685 ◽  
Author(s):  
Cecilia Wallin ◽  
Jinghui Luo ◽  
Jüri Jarvet ◽  
Sebastian K. T. S. Wärmländer ◽  
Astrid Gräslund
Keyword(s):  
Metal Ions ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Formation ◽  
Formation Processes ◽  
Blood Proteins ◽  
Naturally Occurring

scholarly journals Apolipoprotein E Interferes with IAPP Aggregation and Protects Pericytes from IAPP-Induced Toxicity

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 134 ◽  
Author(s):  
Anna L. Gharibyan ◽  
Tohidul Islam ◽  
Nina Pettersson ◽  
Solmaz A. Golchin ◽  
Johanna Lundgren ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Formation ◽  
Loss Of Function ◽  
Islet Amyloid ◽  
Amyloid Deposits ◽  
Primary Focus ◽  
The Impact

Apolipoprotein E (ApoE) has become a primary focus of research after the discovery of its strong linkage to Alzheimer’s disease (AD), where the ApoE4 variant is the highest genetic risk factor for this disease. ApoE is commonly found in amyloid deposits of different origins, and its interaction with amyloid-β peptide (Aβ), the hallmark of AD, is well known. However, studies on the interaction of ApoEs with other amyloid-forming proteins are limited. Islet amyloid polypeptide (IAPP) is an amyloid-forming peptide linked to the development of type-2 diabetes and has also been shown to be involved in AD pathology and vascular dementia. Here we studied the impact of ApoE on IAPP aggregation and IAPP-induced toxicity on blood vessel pericytes. Using both in vitro and cell-based assays, we show that ApoE efficiently inhibits the amyloid formation of IAPP at highly substoichiometric ratios and that it interferes with both nucleation and elongation. We also show that ApoE protects the pericytes against IAPP-induced toxicity, however, the ApoE4 variant displays the weakest protective potential. Taken together, our results suggest that ApoE has a generic amyloid-interfering property and can be protective against amyloid-induced cytotoxicity, but there is a loss of function for the ApoE4 variant.

scholarly journals Aromaticity of Phenylalanine Residues Is Essential for Amyloid Formation by Alzheimer’s Amyloid β-Peptide

2017 ◽  
Vol 65 (7) ◽  
pp. 668-673 ◽  
Author(s):  
Mayumi Genji ◽  
Yoshiaki Yano ◽  
Masaru Hoshino ◽  
Katsumi Matsuzaki
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Formation

scholarly journals Quercetin Disaggregates Prion Fibrils and Decreases Fibril-Induced Cytotoxicity and Oxidative Stress

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1081
Author(s):  
Kun-Hua Yu ◽  
Cheng-I Lee
Keyword(s):  
Oxidative Stress ◽  
Prion Protein ◽  
Amyloid Fibrils ◽  
Neuroblastoma Cells ◽  
Amyloid Β ◽  
Transmissible Spongiform Encephalopathies ◽  
Amyloid Β Peptide ◽  
Hemolysis Assay ◽  
Spongiform Encephalopathies

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases caused by misfolding and aggregation of prion protein (PrP). Previous studies have demonstrated that quercetin can disaggregate some amyloid fibrils, such as amyloid β peptide (Aβ) and α-synuclein. However, the disaggregating ability is unclear in PrP fibrils. In this study, we examined the amyloid fibril-disaggregating activity of quercetin on mouse prion protein (moPrP) and characterized quercetin-bound moPrP fibrils by imaging, proteinase resistance, hemolysis assay, cell viability, and cellular oxidative stress measurements. The results showed that quercetin treatment can disaggregate moPrP fibrils and lead to the formation of the proteinase-sensitive amorphous aggregates. Furthermore, quercetin-bound fibrils can reduce the membrane disruption of erythrocytes. Consequently, quercetin-bound fibrils cause less oxidative stress, and are less cytotoxic to neuroblastoma cells. The role of quercetin is distinct from the typical function of antiamyloidogenic drugs that inhibit the formation of amyloid fibrils. This study provides a solution for the development of antiamyloidogenic therapy.

scholarly journals Rationally Designed Bicyclic Peptides Prevent the Conversion of Aβ42 Assemblies Into Fibrillar Structures

2021 ◽  
Vol 15 ◽  
Author(s):  
Tatsuya Ikenoue ◽  
Francesco A. Aprile ◽  
Pietro Sormanni ◽  
Michele Vendruscolo
Keyword(s):  
Drug Discovery ◽  
Molecular Recognition ◽  
Kinetic Analysis ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Formation ◽  
Aggregation Process ◽  
Structural Studies ◽  
Recognition Ability ◽  
Amyloidogenic Region

There is great interest in drug discovery programs targeted at the aggregation of the 42-residue form of the amyloid β peptide (Aβ42), since this molecular process is closely associated with Alzheimer’s disease. The use of bicyclic peptides may offer novel opportunities for the effective modification of Aβ42 aggregation and the inhibition of its cytotoxicity, as these compounds combine the molecular recognition ability of antibodies with a relatively small size of about 2 kD. Here, to pursue this approach, we rationally designed a panel of six bicyclic peptides targeting various epitopes along the sequence of Aβ42 to scan its most amyloidogenic region (residues 13–42). Our kinetic analysis and structural studies revealed that at sub-stoichiometric concentrations the designed bicyclic peptides induce a delay in the condensation of Aβ42 and the subsequent transition to a fibrillar state, while at higher concentrations they inhibit such transition. We thus suggest that designed bicyclic peptides can be employed to inhibit amyloid formation by redirecting the aggregation process toward amorphous assemblies.

Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein

2005 ◽  
Vol 33 (2) ◽  
pp. 335-338 ◽  
Author(s):  
N.M. Hooper
Keyword(s):  
Amyloid Precursor Protein ◽  
Lipid Rafts ◽  
Prion Protein ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Amyloid Β Peptide ◽  
Copper Binding ◽  
Secretase Activity ◽  
Aβ Amyloid ◽  
A Disintegrin And Metalloproteinase

In the amyloidogenic pathway, the APP (amyloid precursor protein) is proteolytically processed by the β- and γ-secretases to release the Aβ (amyloid-β) peptide that is neurotoxic and aggregates in the brains of patients suffering from Alzheimer's disease. In the non-amyloidogenic pathway, APP is cleaved by α-secretase within the Aβ domain, precluding deposition of intact Aβ peptide. The cellular form of the PrPC (prion protein) undergoes reactive oxygen species-mediated β-cleavage within the copper-binding octapeptide repeats or, alternatively, α-cleavage within the central hydrophobic neurotoxic domain. In addition, PrPC is shed from the membrane by the action of a zinc metalloprotease. Members of the ADAM (a disintegrin and metalloproteinase) family of zinc metalloproteases, notably ADAM10 and TACE (ADAM17) display α-secretase activity towards APP and appear to be responsible for the α-cleavage of PrPC. The amyloidogenic cleavage of APP by the β- and γ-secretases appears to occur preferentially in cholesterol-rich lipid rafts, while the conversion of PrPC into the infectious form PrPSc also appears to occur in these membrane domains.

scholarly journals Metal Ion-dependent Effects of Clioquinol on the Fibril Growth of an Amyloid β Peptide

2005 ◽  
Vol 280 (16) ◽  
pp. 16157-16162 ◽  
Author(s):  
Bakthisaran Raman ◽  
Tadato Ban ◽  
Kei-ichi Yamaguchi ◽  
Miyo Sakai ◽  
Tomoji Kawai ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Metal Ions ◽  
Metal Ion ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Formation ◽  
Metal Chelation ◽  
Comprehensive Understanding ◽  
Aβ Amyloid ◽  
Metal Ion Chelators

Although metal ions such as Cu2+, Zn2+, and Fe3+are implicated to play a key role in Alzheimer disease, their role is rather complex, and comprehensive understanding is not yet obtained. We show that Cu2+and Zn2+but not Fe3+renders the amyloid β peptide, Aβ1–40, nonfibrillogenic in nature. However, preformed fibrils of Aβ1–40were stable when treated with these metal ions. Consequently, fibril growth of Aβ1–40could be switched on/off by switching the molecule between its apo- and holo-forms. Clioquinol, a potential drug for Alzheimer disease, induced resumption of the Cu2+-suppressed but not the Zn2+-suppressed fibril growth of Aβ1–40. The observed synergistic effect of clioquinol and Zn2+suggests that Zn2+-clioquinol complex effectively retards fibril growth. Thus, clioquinol has dual effects; although it disaggregates the metal ion-induced aggregates of Aβ1–40through metal chelation, it further retards the fibril growth along with Zn2+. These results indicate the mechanism of metal ions in suppressing Aβ amyloid formation, as well as providing information toward the use of metal ion chelators, particularly clioquinol, as potential drugs for Alzheimer disease.

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