Journal
MOLECULAR CELL
Volume 63, Issue 5, Pages 768-780Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2016.07.016
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Funding
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- NIH [AG046799, GM065318, A1073847]
- Veterans Administration Research and Development Merit Award [I01 BX002211-01A2]
- NIA [2 P30 AG013319-21]
- Robert L. Bailey and Daughter Lisa K. Bailey Alzheimer's Fund
- William & Ella Owens Medical Research Foundation
- German Research foundation
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Polyphosphate (polyP), a several billion-year-old biopolymer, is produced in every cell, tissue, and organism studied. Structurally extremely simple, polyP consists of long chains of covalently linked inorganic phosphate groups. We report here the surprising discovery that polyP shows a remarkable efficacy in accelerating amyloid fibril formation. We found that polyP serves as an effective nucleation source for various different amyloid proteins, ranging from bacterial CsgA to human alpha-synuclein, A beta(1-40/42), and Tau. polyP-associated alpha-synuclein fibrils show distinct differences in seeding behavior, morphology, and fibril stability compared with fibrils formed in the absence of polyP. In vivo, the amyloid-stimulating and fibril-stabilizing effects of polyP have wide-reaching consequences, increasing the rate of biofilm formation in pathogenic bacteria and mitigating amyloid toxicity in differentiated neuroblastoma cells and C. elegans strains that serve as models for human folding diseases. These results suggest that we have discovered a conserved cytoprotective modifier of amyloidogenic processes.
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