Journal
CHEMICAL COMMUNICATIONS
Volume 59, Issue 98, Pages 14509-14523Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d3cc04138g
Keywords
-
Categories
Ask authors/readers for more resources
This article summarizes the major findings regarding the formation of phenylalanine-based fibrils in aqueous and organic media and discusses the role of non-covalent interactions in the self-assembly process. It is found that phenylalanine-based fibrils are toxic and can induce other neurodegenerative peptides to form toxic fibrils. The article also discusses different approaches to inhibit fibril formation and reduce its toxicity.
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. In this feature article, we discuss the formation of long-range, ordered, amyloid-like fibrils from native phenylalanine molecules in aqueous and organic media and the inhibition of toxic fibrils by using various potent therapeutic agents.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available