Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo

Abstract

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

Controversial Properties of Amyloidogenic Proteins and Peptides: New Data in the COVID Era

“…New findings point to a delicate communication between the viral and host proteomes after infection, including the cross-seeding of host proteins by viral proteins [ 19 , 78 , 79 , 80 , 81 , 82 , 83 , 87 , 88 ].…”

“…These results suggest the existence of direct interactions and cross-seeding ( Figure 2 ) between the N-protein of SARS-CoV-2 and α-synuclein which serve as the molecular basis for the association between SARS-CoV-2 infections and Parkinson’s disease [ 80 ]. Currently, various models have been proposed [ 81 ] and further studies are needed to clarify the exact mechanism of cross-seeding.…”

“…SARS-CoV-2 proteins interact with the negatively charged C-terminal region of α-synuclein which speeds up the misfolding and fibrosis of α-synuclein [ 80 , 81 ]. According to theoretical bioinformatic prediction, the S-protein contains several amyloidogenic amino acid sequences.…”

Computational Investigation of Coaggregation and Cross-Seeding between Aβ and hIAPP Underpinning the Cross-Talk in Alzheimer’s Disease and Type 2 Diabetes

“…18 Increasing evidence suggests that the cross-talk between the colocalized Aβ and hIAPP might play a pivotal role in linking AD and T2D clinically. 11,14,19,20 Aβ peptides, primarily derived from the cleavage of the amyloid precursor protein by βand γ-secretases in the human brain, mainly constitute senile plaques in AD. 5 These plaques predominantly comprise Aβ40 and Aβ42 isoforms, with Aβ42 exhibiting heightened aggregation and toxicity.…”

“…22,23 For both Aβ and hIAPP, whether in fragments and full-length forms, the formation of β-barrel intermediates during their aggregation has been reported. 4,6,8,24,26 Considering the coexistence of hIAPP and Aβ in the human brain and pancreas, 11,15−17 alongside the clinical overlaps between AD and T2D, 15,19 extensive studies have investigated the interplay between these peptides, encompassing coaggregation and cross-seeding phenomena. 19,27 hIAPP aggregates more rapidly than Aβ at equivalent concentrations, displaying significantly shorter lag phases in vitro.…”