Metal ions, including copper and zinc, have been implicated in the pathogenesis of Alzheimer's disease through a variety of mechanisms including increased amyloid-β affinity and redox effects. Recent reports have demonstrated that the amyloid-β monomer does not necessarily travel through a definitive intermediary en-route to a stable amyloid fibril structure. Rather, amyloid-β misfolding may fo...

The current dominant theory of Alzheimer’s disease (AD) etiology and pathogenesis is related to the amyloid cascade hypothesis which states that overproduction of amyloid-beta-peptide (AβP), or failure to clear this peptide, leads to Alzheimer’s disease primarily through amyloid deposition, presumed to be involved in neurofibrillary tangles formation [1]. Amyloid-β (Aβ) plaque formation, one of...

A purpose-designed porphyrin-peptide hybrid effectively degraded amyloid β monomer and oligomers associated with Alzheimer's disease. Degradation was achieved using light irradiation in the absence of any additives and under neutral conditions. Moreover, the hybrid effectively neutralized the cytotoxicity of amyloid β in PC12 cells upon photoirradiation.

The early oligomers of the amyloid Aβ peptide are implicated in Alzheimer’s disease, but their transient nature complicates characterization structure and toxicity. Here, we investigate stability minimal toxic species, i.e., β-amyloid dimers, presence an oscillating electric field. We first use deep learning (AlphaFold-multimer) for generating initial models Aβ42 dimers. flexibility secondary c...

Amyloid formation has been implicated in the pathology of over 20 human diseases, but the rational design of amyloid inhibitors is hampered by a lack of structural information about amyloid-inhibitor complexes. We use isotope labelling and two-dimensional infrared spectroscopy to obtain a residue-specific structure for the complex of human amylin (the peptide responsible for islet amyloid forma...

BACKGROUND Misfolding and self-assembly of Amyloid-β (Aβ) peptides into amyloid fibrils is pathologically linked to the development of Alzheimer's disease. Polymorphic Aβ structures derived from monomers to intermediate oligomers, protofilaments, and mature fibrils have been often observed in solution. Some aggregates are on-pathway species to amyloid fibrils, while the others are off-pathway s...

The soluble fraction of brain samples from patients with Alzheimer's disease contains highly biologically active amyloid-β seeds. In this study, we sought to assess the potency of soluble amyloid-β seeds derived from the brain and cerebrospinal fluid. Soluble Alzheimer's disease brain extracts were serially diluted and then injected into the hippocampus of young, APP transgenic mice. Eight mont...

Amyloid formation in the pancreatic islets due to aggregation of human islet amyloid polypeptide (hIAPP) contributes to reduced β-cell mass and function in type 2 diabetes (T2D) and islet transplantation. Protein kinase B (PKB) signaling plays a key role in the regulation of β-cell survival, function and proliferation. In this study, we used human and hIAPP-expressing transgenic mouse islets in...

The amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD). APP can undergo two exclusive proteolytic pathways: cleavage by the α-secretase initiates the non-amyloidogenic pathway while cleavage by the β-secretase initiates the amyloidogenic pathway that leads, after a second cleavage by the γ-secretase, to amyloid-β (Aβ) peptides that can form toxic extracellular depo...