Recent developments in the chemical biology of amyloid-β oligomer targeting

Abstract

Aggregation of amyloid-β (Aβ) peptides is characteristic of Alzheimer’s disease (AD), which is the most common neurodegenerative disorder. Increasing evidence shows that Aβ oligomers, the intermediates during aggregation, rather than...

Recent progress of small-molecule-based theranostic agents in Alzheimer's disease

“…Aβ oligomers as both biomarkers and therapeutic targets have attracted more and more attention for the diagnosis and treatment of early AD. 7 The development of small-molecule-based probes that can precisely recognize Aβ oligomers in the specific aggregation state would dramatically benefit the personalized treatment of AD. (ii) Synergistic effect between the diagnosis and therapeutic moieties.…”

“…31 Accordingly, Aβ aggregates, especially oligomers (the most toxic Aβ species) and fibrils, have been considered as drug targets for AD treatment. 7 Similar to Aβ, ptau would be another potential target according to the tau hypothesis, which states that the aggregation of ptau can lead to AD through destroying neuronal functions. 19,32,33 Therefore, Aβ and ptau aggregates as both biomarkers and pathological factors can be potential targets for the design of small-molecule-based theranostic agents.…”

“…4,5 The USA FDA approved two anti-amyloid monoclonal antibodies, aducanumab and lecanemab, for disease-modifying therapy of AD in 2021 and 2023, respectively. 6–8 However, these recent approvals are fraught with controversy due to the safety concerns associated with these antibodies. For example, they may weaken the blood vessels to worsen the brain bleeding.…”

Early Diagnosis of Neurodegenerative Diseases: What Has Been Undertaken to Promote the Transition from PET to Fluorescence Tracers

“…In this review, we aim to provide a general overview of the main achievements in the development of fluorescent probes for the detection of amyloid aggregates in the frame of AD and PD. Since a significant number of reports have already been published for the Aβ 1-42 peptide [49][50][51], this review will firstly show the main advantages and disadvantages of the approaches currently reported for the design of fluorescent probes detecting Aβ 1-42 toxic oligomers. Afterwards, a discussion in the same regard will be dedicated to the Tau protein, whose detection is still under research investigation, especially for the validation of biomarkers' outcomes.…”

Detection and disaggregation of amyloid fibrils by luminescent amphiphilic platinum(ii) complexes

“…As a result, other organic fluorophores have been investigated as probes for amyloid fibrils, 17–20 and a much smaller subset of compounds has been shown to respond to the presence of soluble amyloid oligomers. 21–32 From these studies common structural features of probe molecules that promote binding to amyloid aggregates have been identified. The most important of these is the presence of extended hydrophobic surfaces, such as found in biaryl, polyaryl, polyaromatic, and stilbene-like fragments, that can interact with exposed hydrophobic sites on amyloid fibrils and oligomers.…”