Melanin Suppresses Aβ Aggregation and Toxicity
- 1Yusuf Hamied Department of Chemistry, University of Cambridge
Abstract
The aggregation of amyloid-{beta} (A{beta}) peptides into insoluble deposits is a characteristic hallmark of Alzheimer's disease (AD) and related neurodegenerative disorders. While AD is the most common cause of dementia, there are currently no disease-modifying treatments which are both affordable and adverse-free. In this study, we report that melanin, a pigment which is commonly found in nature and is abundant in parts of the human brain, suppresses the aggregation of the 42-amino acid A{beta} variant (A{beta}42). Using biophysical and biochemical techniques, we show that melanin delays A{beta}42 aggregation while also reducing the amount of A{beta}42 that converts into aggregates. Using thioflavin T assays paired with chemical kinetics, we characterised the melanin-induced inhibition of A{beta}42 aggregation in vitro. Using MALDI-MS, we elucidate the molecular basis of this effect by showing that melanin prevents A{beta}42 dimerisation. We then demonstrate that melanin also reverts the aggregation process by dissolving pre-formed A{beta}42 fibrils. Finally, we show that melanin reduces A{beta}42 aggregation and rescues A{beta}42 toxicity in an SH-SY5Y neuroblastoma cell model. Our study shows that melanin disrupts the aggregation and cytotoxicity of A{beta}42, and suggests that compounds derived from human metabolites may offer promising avenues to combat amyloid formation.
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BibTeX
@misc{rontgen2026melanin,
title = {{Melanin Suppresses Aβ Aggregation and Toxicity}},
author = {A. Röntgen and J. L. Heise and M. Vendruscolo and Z. Toprakcioglu},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748646},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748646v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Melanin Suppresses Aβ Aggregation and Toxicity
AU - A. Röntgen
AU - J. L. Heise
AU - M. Vendruscolo
AU - Z. Toprakcioglu
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748646
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748646v1
AB - The aggregation of amyloid-{beta} (A{beta}) peptides into insoluble deposits is a characteristic hallmark of Alzheimer's disease (AD) and related neurodegenerative disorders. While AD is the most common cause of dementia, there are currently no disease-modifying treatments which are both affordable and adverse-free. In this study, we report that melanin, a pigment which is commonly found in nature and is abundant in parts of the human brain, suppresses the aggregation of the 42-amino acid A{beta} variant (A{beta}42). Using biophysical and biochemical techniques, we show that melanin delays A{beta}42 aggregation while also reducing the amount of A{beta}42 that converts into aggregates. Using thioflavin T assays paired with chemical kinetics, we characterised the melanin-induced inhibition of A{beta}42 aggregation in vitro. Using MALDI-MS, we elucidate the molecular basis of this effect by showing that melanin prevents A{beta}42 dimerisation. We then demonstrate that melanin also reverts the aggregation process by dissolving pre-formed A{beta}42 fibrils. Finally, we show that melanin reduces A{beta}42 aggregation and rescues A{beta}42 toxicity in an SH-SY5Y neuroblastoma cell model. Our study shows that melanin disrupts the aggregation and cytotoxicity of A{beta}42, and suggests that compounds derived from human metabolites may offer promising avenues to combat amyloid formation.
ER -