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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish
Article number170229
JournalOpen Biology
Issue number1
StatePublished - 2018


FundersFunder number
Israel Science Foundation802/15


    • Amyloid seeding
    • Inborn error of metabolism
    • Mechanism of neurodegeneration
    • Metabolite accumulation
    • Metabolite amyloids
    • Oncometabolites


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