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 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.

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

scholarly journals Conformational Regulation of Amyloid β-peptide by Lipid Membranes and Metal Ions

2010 ◽  
Vol 130 (4) ◽  
pp. 495-501 ◽  
Author(s):  
Takashi MIURA ◽  
Mayumi YODA ◽  
Chihiro TSUTSUMI ◽  
Kiyoko MURAYAMA ◽  
Hideo TAKEUCHI
Keyword(s):  
Metal Ions ◽  
Lipid Membranes ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Conformational Regulation

ChemInform Abstract: Biophysical Studies of the Amyloid β-Peptide: Interactions with Metal Ions and Small Molecules

ChemInform ◽  
2013 ◽  
Vol 44 (47) ◽  
pp. no-no
Author(s):  
Sebastian Waermlaender ◽  
Ann Tiiman ◽  
Axel Abelein ◽  
Jinghui Luo ◽  
Jyri Jarvet ◽  
...  
Keyword(s):  
Metal Ions ◽  
Small Molecules ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Peptide Interactions ◽  
Biophysical Studies

Biophysical Studies of the Amyloid β-Peptide: Interactions with Metal Ions and Small Molecules

ChemBioChem ◽  
2013 ◽  
Vol 14 (14) ◽  
pp. 1692-1704 ◽  
Author(s):  
Sebastian Wärmländer ◽  
Ann Tiiman ◽  
Axel Abelein ◽  
Jinghui Luo ◽  
Jyri Jarvet ◽  
...  
Keyword(s):  
Metal Ions ◽  
Small Molecules ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Peptide Interactions ◽  
Biophysical Studies

scholarly journals Immunotherapeutic Strategies for Alzheimer's Disease Treatment

2009 ◽  
Vol 9 ◽  
pp. 909-919 ◽  
Author(s):  
Beka Solomon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Passive Immunization ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Disease Treatment ◽  
Naturally Occurring ◽  
Age Related ◽  
The Central Nervous System ◽  
Naturally Occurring Antibodies

Naturally occurring antibodies against amyloid-β peptides have been found in human cerebrospinal fluid and in the plasma of healthy individuals, but were significantly lower in Alzheimer's disease (AD) patients, suggesting that AD may be an immunodeficient disorder. The performance of anti-amyloid-β antibodies in transgenic mice models of AD showed that they are delivered to the central nervous system, preventing and dissolving amyloid-β plaques. Moreover, these antibodies protected the mice from learning and age-related memory deficits. Active and/or passive immunization against the amyloid-β peptide has been proposed as a method for preventing and/or treating AD. Immunotherapy represents fascinating ways to test the amyloid hypothesis and offers genuine opportunities for AD treatment, but requires careful antigen and antibody selection to maximize efficacy and minimize adverse events.

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.

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