scholarly journals Functional Switching of a Native Neuropeptide Through Interactions with Pathogenic Factors in Dementia

2021 ◽  
Author(s):  
Jiyeon Han ◽  
Eunju Nam ◽  
Jiwon Yoon ◽  
Tongrui Qian ◽  
Yulong Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ions ◽  
Amyloid Beta ◽  
Conformational Transition ◽  
Metal Free ◽  
Pathogenic Factors ◽  
Functional Switching

We discovered that the function of a native neuropeptide, somatostatin (SST), is switched through its conformational transition in the presence of metal ions, metal-free amyloid-beta (Abeta), and metal-bound Abeta that are associated with toxicity observed in the brains of Alzheimer’s disease patients.

scholarly journals Functional Switching of a Native Neuropeptide Through Interactions with Pathogenic Factors in Dementia

2021 ◽  
Author(s):  
Jiyeon Han ◽  
Eunju Nam ◽  
Jiwon Yoon ◽  
Tongrui Qian ◽  
Yulong Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ions ◽  
Amyloid Beta ◽  
Conformational Transition ◽  
Metal Free ◽  
Pathogenic Factors ◽  
Functional Switching

We discovered that the function of a native neuropeptide, somatostatin (SST), is switched through its conformational transition in the presence of metal ions, metal-free amyloid-beta (Abeta), and metal-bound Abeta that are associated with toxicity observed in the brains of Alzheimer’s disease patients.

Molecular dynamic studies of amyloid-beta interactions with curcumin and Cu2+ ions

2015 ◽  
Vol 69 (9) ◽  
Author(s):  
Stanislav Kozmon ◽  
Igor Tvaroška
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Dynamics ◽  
Transition Metals ◽  
Metal Ions ◽  
Molecular Dynamic ◽  
Amyloid Beta ◽  
Md Simulations ◽  
Aβ Peptide ◽  
Dynamic Studies

AbstractAmyloid-beta (Aβ) peptide readily forms aggregates that are associated with Alzheimer’s disease. Transition metals play a key role in this process. Recently, it has been shown that curcumin (CUA), a polyphenolic phytochemical, inhibits the aggregation of Aβ peptide. However, interactions of Aβ peptide with metal ions or CUA are not entirely clear. In this work, molecular dynamics (MD) simulations were carried out to clear the nature of interactions between the 42-residue Aβ peptide (Aβ-42) and Cu

Ruthenium(II)–arene complexes with chelating quinoline ligands as anti-amyloid agents

2021 ◽  
pp. 1-7
Author(s):  
Cade J. Meiss ◽  
Paige J. Bothwell ◽  
Michael I. Webb
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ions ◽  
Amyloid Beta ◽  
The Other ◽  
Soluble Form ◽  
Aβ Peptide ◽  
Arene Complexes ◽  
Therapeutic Development ◽  
Neurotoxic Agent

Recent recognition of the soluble form of the amyloid-beta (Aβ) peptide as a neurotoxic agent in Alzheimer’s disease (AD) has spurred the development of agents to target this species. Because Aβ is known to chelate metal ions in solution, metal-based therapeutics are uniquely suited to exploit this affinity, where coordination to Aβ has been shown to impact the neurotoxicity of the peptide. Ruthenium(II)–arene complexes are unique candidates for evaluation, as one face of the molecule is blocked by the hydrophobic arene ring, while coordination to the Aβ peptide can occur on the other side of the molecule. We have prepared and evaluated two Ru(II)–arene complexes with chelating quinoline-based ligands, Ru1 and Ru2, for their respective anti-amyloid abilities. Although both complexes decreased the aggregation of soluble Aβ, Ru1 displayed promise in disrupting formed aggregates of the peptide. These findings represent an exciting new avenue for therapeutic development in AD, where both sides of the aggregation equilibrium are affected.

Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's disease

2002 ◽  
Vol 38 ◽  
pp. 37-49 ◽  
Author(s):  
Janelle Nunan ◽  
David H Small
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Alternative Pathway ◽  
Protein A ◽  
Proteolytic Processing ◽  
Gamma Secretase ◽  
Amyloid Beta Protein ◽  
Protein Precursor ◽  
Amyloid Beta Protein Precursor

The proteolytic processing of the amyloid-beta protein precursor plays a key role in the development of Alzheimer's disease. Cleavage of the amyloid-beta protein precursor may occur via two pathways, both of which involve the action of proteases called secretases. One pathway, involving beta- and gamma-secretase, liberates amyloid-beta protein, a protein associated with the neurodegeneration seen in Alzheimer's disease. The alternative pathway, involving alpha-secretase, precludes amyloid-beta protein formation. In this review, we describe the progress that has been made in identifying the secretases and their potential as therapeutic targets in the treatment or prevention of Alzheimer's disease.

Minimalistic Design Approach for Multi-Reactivity against Free Radicals and Metal-Free and Metal-Bound Amyloid-β Peptides: Redox-Based Substitutions of Benzene

2019 ◽  
Author(s):  
Mingeun Kim ◽  
Juhye Kang ◽  
Misun Lee ◽  
Jiyeon Han ◽  
Geewoo Nam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radicals ◽  
Amyloid Β ◽  
Design Strategy ◽  
Design Approach ◽  
Metal Free

We report a minimalistic redox-based design strategy for engineering compact molecules based on the simplest aromatic framework, benzene, with multi-reactivity against free radicals, metal-free amyloid-β, and metal-bound amyloid-β, implicated in the most common form of dementia, Alzheimer’s disease.

Sign in / Sign up

Export Citation Format

Share Document