Seeding of proteins into amyloid structures by metabolite assemblies may clarify certain unexplained epidemiological associations

Dorin Sade, Shira Shaham-Niv, Zohar A. Arnon, Omid Tavassoly, Ehud Gazit

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

תקציר

The accumulation of various metabolites appears to be associated with diverse human diseases. However, the aetiological link between metabolic alteration and the observed diseases is still elusive. This includes the correlation between the abnormally high levels of homocysteine and quinolinic acid in Alzheimer's disease, aswell as the accumulation of oncometabolites in malignant processes. Here, we suggest and discuss a possible mechanistic insight into metabolite accumulation in conditions such as neurodegenerative diseases and cancer. Our hypothesis is based on the demonstrated ability of metabolites to form amyloid-like structures in inborn error of metabolism disorders and the potential of such metabolite amyloids to promote protein aggregation. This notion can provide a new paradigm for neurodegeneration and cancer, as both conditions were linked to loss of function due to protein aggregation. Similar to the wellestablished observation of amyloid formation in many degenerative disorders, the formation of amyloids by tumour-suppressor proteins, including p53, was demonstrated in malignant states. Moreover, this new paradigm could fill the gap in understanding the high occurrence of specific types of cancer among genetic error of metabolism patients. This hypothesis offers a fresh view on the aetiology of some of the most abundant human maladies and may redirect the efforts towards new therapeutic developments.

שפה מקוריתאנגלית
מספר המאמר170229
כתב עתOpen Biology
כרך8
מספר גיליון1
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 2018

ASJC Scopus subject areas

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טביעת אצבע

להלן מוצגים תחומי המחקר של הפרסום 'Seeding of proteins into amyloid structures by metabolite assemblies may clarify certain unexplained epidemiological associations'. יחד הם יוצרים טביעת אצבע ייחודית.

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