A new era for understanding amyloid structures and disease

@article{Iadanza2018ANE,
  title={A new era for understanding amyloid structures and disease},
  author={Matthew G. Iadanza and Matthew P. Jackson and Eric W. Hewitt and Neil A. Ranson and Sheena E. Radford},
  journal={Nature Reviews Molecular Cell Biology},
  year={2018},
  volume={19},
  pages={755-773}
}
The aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions is the hallmark of amyloid disease. The accumulation and deposition of amyloid fibrils, collectively known as amyloidosis, is associated with many pathological conditions that can be associated with ageing, such as Alzheimer disease, Parkinson disease, type II diabetes and dialysis-related amyloidosis. However, elucidation of the atomic structure of amyloid fibrils formed from their… 
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Defects in protein folding and/or quality control cause protein aggregation in the ER
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References

SHOWING 1-10 OF 335 REFERENCES
Direct visualisation of the beta-sheet structure of synthetic Alzheimer's amyloid.
TLDR
The core structure of an Alzheimer's amyloid fibril is revealed by direct visualisation using cryo-electron microscopy to help understand the abnormal assembly and deposition of these fibrils and could lead to the rational design of therapeutic agents for their prevention or disaggregation.
Amyloid plaque structure and cell surface interactions of β-amyloid fibrils revealed by electron tomography
TLDR
It is shown here that amyloid formation in the cell model functionally destroys the integrity of the intracellular membranes as it leads to lysosomal leakage, providing a mechanistic link to explain why intrACEllular fibril formation is toxic to the cell.
Functional Amyloid Formation within Mammalian Tissue
TLDR
The discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17 is reported, demonstrating thatAmyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans and mitigating the toxicity associated with melanin formation.
Toxic species in amyloid disorders: Oligomers or mature fibrils
TLDR
The difference in structure and proposed toxicity pathways for fibrils and oligomers, and the evidences indicating that intermediary oligomeric species can act as potential diagnostic biomarker for these toxic amyloid species are highlighted.
Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril
TLDR
The 3D structure of a disease-relevant Aβ(1–42) fibril polymorph is determined combining data from solid-state NMR spectroscopy and mass-per-length measurements from EM, forming a double-horseshoe–like cross–β-sheet entity with maximally buried hydrophobic side chains.
Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade.
TLDR
This review describes this field of science with particular reference to the advances that have been made over the last decade in understanding of its fundamental nature and consequences and shows evidence that a complex proteostasis network actively combats protein aggregation.
A Common β-Sheet Architecture Underlies in Vitro and in Vivo β2-Microglobulin Amyloid Fibrils*S⃞
TLDR
Amyloid-like fibrils formed in vitro from natively folded or unfolded β2-microglobulin (the protein associated with dialysis-related amyloidosis) adopt an identical β-sheet architecture, and the same β-strand signature is observed whether fibril formation in vitro occurs spontaneously or from seeded reactions.
In situ measurements of the formation and morphology of intracellular β-amyloid fibrils by super-resolution fluorescence imaging.
TLDR
The data support the recent view that intracellular Aβ could be associated with Aβ pathogenicity in AD, although the major deposits are extracellular, and suggest that this approach will be widely applicable to studies of the molecular mechanisms of protein deposition diseases.
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