Aggregation propensity of neuronal receptors: Potential implications in neurodegenerative disorders

Susanna Navarro, Marta Diaz-Caballero, Ricard Illa, Salvador Ventura

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

© Salvador Ventura. Misfolding and aggregation of proteins in tissues is linked to the onset of a diverse set of human neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. In these pathologies proteins usually aggregate into highly ordered and β-sheet enriched amyloid fibrils. However, the formation of these toxic structures is not restricted to a reduced set of polypeptides but rather an intrinsic property of proteins. This suggests that the number of proteins involved in conformational disorders might be much larger than previously thought. The propensity of a protein to form amyloid assemblies is imprinted in its sequence and can be read using computational approaches. Here, we exploit four of these algorithms to analyze the presence of aggregation-prone regions in the sequence and structure of the extracellular domains of several neuroreceptors, with the idea of identifying patches that can interact anomalously with other aggregation-prone molecules such as the amyloid-β peptide or promote their self-assembly. The number of amyloidogenic regions in these domains is rather low but they are significantly exposed to solvent and therefore are suitable for interactions. We find a significant overlap between aggregation-prone regions and receptors interfaces and/or ligand-binding sites, which illustrates an unavoidable competition between the formation of functional native interactions and that of dangerous amyloid-like contacts leading to disease.
Original languageEnglish
Article numberFSO39
JournalFuture Science OA
Volume1
Issue number2
DOIs
Publication statusPublished - 1 Sep 2015

Keywords

  • Alzheimer's disease
  • aggregation-prone regions
  • amyloid
  • neurodegenerative disorders
  • neuronal receptor

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