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Open AccessCommunication

Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the Assemblies

1
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
2
Department of Materials Science and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 6997801, Israel
3
BLAVATNIK CENTER for Drug Discovery, Tel Aviv University, Tel Aviv 6997801, Israel
*
Author to whom correspondence should be addressed.
Molecules 2018, 23(6), 1273; https://doi.org/10.3390/molecules23061273
Received: 1 April 2018 / Revised: 10 May 2018 / Accepted: 23 May 2018 / Published: 26 May 2018
(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)
The amino acid tyrosine forms cytotoxic amyloid-like fibrils by molecular self-assembly. However, the production of antibodies towards tyrosine assemblies, reflecting their presentation to the immune system, was not demonstrated yet. Here, we describe the production of antibodies that specifically recognize tyrosine in its fibrillated form. The antibodies were demonstrated to specifically bind self-assembled tyrosine, in contrast to its non-aggregated form or disintegrated fibrils. The antibodies could be used for immunostaining of tyrosine fibrils in cultured cells. Furthermore, confocal microscopy allowed a demonstration of the intracellular presence of the metabolite amyloids in a neuroblastoma cell model. Finally, pre-incubation of tyrosine fibrils with the antibodies resulted in significant reduction in their cytotoxicity. Taken together, we provide an experimental proof for the immunogenicity of tyrosine amyloid fibrillary assemblies. These specific antibodies against tyrosine structures could be further used as a research tool to study the dynamics, toxicity and cellular localization of the assemblies. View Full-Text
Keywords: self-assembly; tyrosine; metabolite amyloid-like fibrils; tyrosinemia; inborn error of metabolism; immunogenicity; anti-tyr antibodies self-assembly; tyrosine; metabolite amyloid-like fibrils; tyrosinemia; inborn error of metabolism; immunogenicity; anti-tyr antibodies
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MDPI and ACS Style

Zaguri, D.; Kreiser, T.; Shaham-Niv, S.; Gazit, E. Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the Assemblies. Molecules 2018, 23, 1273.

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