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Review
. 2023 Dec 7;59(98):14509-14523.
doi: 10.1039/d3cc04138g.

Phenylalanine-based fibrillar systems

Soumen Kuila  1 , Sukantha Dey  1 , Pijush Singh  1   2 , Akash Shrivastava  1 , Jayanta Nanda  1
Affiliations
Review

Phenylalanine-based fibrillar systems

Soumen Kuila et al. Chem Commun (Camb). .

Abstract

Phenylketonuria (PKU) is an inborn metabolic disorder characterized by excess accumulation of phenylalanine (Phe) and its fibril formation, resulting in progressive intellectual disability. Several research groups have approached from various directions to understand the formation of toxic amyloid fibrils from the essential amino acid Phe. Different parameters like the nature of the solvent, pH, Phe concentration, temperature, etc. influence the fibril formation kinetics. In this article, we have summarized all major findings regarding the formation of Phe-based fibrils in aqueous and organic media and discussed how non-covalent interactions are involved in the self-assembly process using spectroscopic and microscopic techniques. The toxicity of Phe-based fibrils is compared with other neurodegenerative peptides. It is noted that the Phe-based fibrils can also induce various globular proteins into toxic fibrils. Later, we discuss the different approaches to inhibit fibril formation and reduce its toxicity. The presence of polyphenolic compounds, drugs, amino acids, nanoparticles, metal ions, crown ethers, and others showed a remarkable inhibitory effect on fibril formation. To the best of our knowledge, this is the first-ever etymological analysis of the Phe-fibrillar system and its inhibition to create a strong database against PKU.

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