Catalytic-Defect Passivation on Amyloid-β Fibrils Using Atomically Precise Gold Nanoclusters
4 affiliations
- 1Department of Neuroscience and Regenerative Medicine
- 2Augusta University
- 3Nanoscience Center
- 4University of Jyväskylä
Abstract
Most pharmacological strategies targeting amyloid-β (Aβ) in Alzheimer’s disease have focused on reducing Aβ production, preventing aggregation, or removing deposited amyloid from the brain. Within the Aβ aggregation pathway, secondary nucleation is a critical amplification step in which pre-existing fibrils catalyze the formation of new aggregates on their surfaces. Some of these aggregates detach and grow into additional fibrils, sustaining an autocatalytic cycle that makes secondary nucleation an attractive target for pharmacological intervention. Biophysical studies indicate that rare defects formed during fibril growth act as hotspots for secondary nucleation, and that fibrils with fewer such defects show markedly lower secondarynucleation activity. Therefore, these findings raise the possibility that defect passivation could reduce the catalytic activity of Aβ fibrils without requiring their removal. This topical review proposes atomically precise, ligand-protected gold nanoclusters (AuNCs) as a tunable platform for selectively targeting and blocking these catalytic defects. Taking advantage of their welldefined metal cores and customizable ligand layers, we outline how AuNCs can be engineered for selective recognition of fibril surfaces and catalytic inhibition. We introduce an inversedesign strategy that integrates molecular modeling with machine learning-guided screening to identify optimal AuNC candidates before validating them through aggregation kinetics and neuronal assays. Defect-selective passivation would offer a distinct anti-amyloid approach by suppressing the critical autocatalytic amplification step of Aβ aggregation rather than removing deposited amyloid.
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BibTeX
@misc{cisterna2026catalyticdefect,
title = {{Catalytic-Defect Passivation on Amyloid-β Fibrils Using Atomically Precise Gold Nanoclusters}},
author = {Bruno A. Cisterna and María Francisca Matus},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009508/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009508/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Catalytic-Defect Passivation on Amyloid-β Fibrils Using Atomically Precise Gold Nanoclusters
AU - Bruno A. Cisterna
AU - María Francisca Matus
PY - 2026
DA - 2026/09/27
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009508/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009508/v1
AB - Most pharmacological strategies targeting amyloid-β (Aβ) in Alzheimer’s disease have focused on reducing Aβ production, preventing aggregation, or removing deposited amyloid from the brain. Within the Aβ aggregation pathway, secondary nucleation is a critical amplification step in which pre-existing fibrils catalyze the formation of new aggregates on their surfaces. Some of these aggregates detach and grow into additional fibrils, sustaining an autocatalytic cycle that makes secondary nucleation an attractive target for pharmacological intervention. Biophysical studies indicate that rare defects formed during fibril growth act as hotspots for secondary nucleation, and that fibrils with fewer such defects show markedly lower secondarynucleation activity. Therefore, these findings raise the possibility that defect passivation could reduce the catalytic activity of Aβ fibrils without requiring their removal. This topical review proposes atomically precise, ligand-protected gold nanoclusters (AuNCs) as a tunable platform for selectively targeting and blocking these catalytic defects. Taking advantage of their welldefined metal cores and customizable ligand layers, we outline how AuNCs can be engineered for selective recognition of fibril surfaces and catalytic inhibition. We introduce an inversedesign strategy that integrates molecular modeling with machine learning-guided screening to identify optimal AuNC candidates before validating them through aggregation kinetics and neuronal assays. Defect-selective passivation would offer a distinct anti-amyloid approach by suppressing the critical autocatalytic amplification step of Aβ aggregation rather than removing deposited amyloid.
ER -