The amyloid interactome: Exploring protein aggregation

Abstract

Protein-protein interactions are the quintessence of physiological activities, but also participate in pathological conditions. Amyloid formation, an abnormal protein-protein interaction process, is a widespread phenomenon in divergent proteins and peptides, resulting in a variety of aggregation disorders. The complexity of the mechanisms underlying amyloid formation/amyloidogenicity is a matter of great scientific interest, since their revelation will provide important insight on principles governing protein misfolding, self-assembly and aggregation. The implication of more than one protein in the progression of different aggregation disorders, together with the cited synergistic occurrence between amyloidogenic proteins, highlights the necessity for a more universal approach, during the study of these proteins. In an attempt to address this pivotal need we constructed and analyzed the human amyloid interactome, a protein-protein interaction network of amyloidogenic proteins and their experimentally verified interactors. This network assembled known interconnections between well-characterized amyloidogenic proteins and proteins related to amyloid fibril formation. The consecutive extended computational analysis revealed significant topological characteristics and unraveled the functional roles of all constituent elements. This study introduces a detailed protein map of amyloidogenicity that will aid immensely towards separate intervention strategies, specifically targeting sub-networks of significant nodes, in an attempt to design possible novel therapeutics for aggregation disorders.

P53 aggregation, interactions with tau, and impaired DNA damage response in Alzheimer’s disease

“…The gradual cell death seen in AD has been historically attributed to tau and amyloid-β protein aggregation, forming the hallmark neurofibrillary tangles (NFTs) and plaques, respectively, seen in AD [ 41 , 60 ]. However, recent studies suggest that other essential proteins form aggregates that may interact and contribute to toxicity [ 11 , 43 , 86 , 110 ].…”

Cystatin C regulates the cytotoxicity of infection‐induced endothelial‐derived β‐amyloid

“…6). Previous published studies have identified an entire cohort of interacting proteins that modulate Ab toxicity [22]. Mass spectrometry of PA103 supernatant was performed to determine whether any of these reported modulators are released from endothelial cells during infection processes as co-immunoprecipitation of one or more of these proteins may explain why depletion of Ab led to increased cytotoxic activity.…”

Visualization and Analysis of the Interaction Network of Proteins Associated with Blood-cell targeting Autoimmune Diseases

“…Several studies have proved that MCL effectively identifies high-quality functional modules (47,48), and produces more accurate results for biological networks (49,50). The inflation value of MCL was set to 1.8, in compliance with other analyses that proved this value as suitable for biological networks (47,51,52).…”