High pressure studies on the misfolding and aggregation of p53 in cancer and of α-synuclein in Parkinson’s disease

ABSTRACT

High pressure research can be used to aid in answering why some polypeptide chains reversibly unfold and others adopt a misfolding conformation culminating in aggregation. This topic is one of the fundamental questions in biology that we seek to understand, and for that, we have been experimentally applying pressure to proteins for the last 20 years. Here, we exemplify how pressure research should be used to identify preamyloidogenic protein intermediates as well as to dissociate supramolecular complexes. We believe that the applications of high pressure to understand the behavior of proteins are diverse and can help biologists answer fundamental questions of biomedical relevance.

KEYWORDS:

• p53
• alpha-synuclein
• protein folding
• neurodegenerative disorders
• cancer

Acknowledgements

Our laboratories were supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq awards and the INCT Program), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).All authors contributed to writing this manuscript. All authors approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

ORCID

Jerson L. Silva http://orcid.org/0000-0001-9523-9441

Additional information

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq): [Grant Number 402321/2016-2, INCT 465395/2014-7]; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ): [Grant Number FAPERJ 210008/2018].