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Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
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The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
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Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
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Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
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Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast
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Cyclodextrins promote protein aggregation posing risks for therapeutic applications.

Min S Wang1, Shanta Boddapati, Michael R Sierks

  • 1Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287-6006, USA.

Biochemical and Biophysical Research Communications
|June 23, 2009
PubMed
Summary

Cyclodextrins alter beta-amyloid aggregation, potentially increasing toxicity in brain diseases like Alzheimer's. Caution is advised when using cyclodextrins for blood-brain barrier delivery or neurological treatments.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Neurofibrillary tangles (NFTs) are key in neurodegenerative diseases like Alzheimer's (AD).
  • Elevated cholesterol is linked to NFTs, and cyclodextrins manage cholesterol in Niemann-Pick C disease models.
  • Cyclodextrins are explored as drug carriers across the blood-brain barrier (BBB).

Purpose of the Study:

  • To investigate the impact of cyclodextrins on beta-amyloid (Abeta) aggregation.
  • To assess how cyclodextrins affect the toxicity of Abeta, a protein implicated in AD.

Main Methods:

  • Studied the aggregation kinetics of Abeta in the presence of cyclodextrins.
  • Examined morphological changes in Abeta aggregates induced by cyclodextrins.
  • Assessed the toxicity of cyclodextrin-modified Abeta on SH-SY5Y neuroblastoma cells.

Main Results:

  • Cyclodextrins significantly altered Abeta aggregation rates.
  • Cyclodextrins induced morphological changes in Abeta aggregates.
  • These modified Abeta aggregates exhibited enhanced toxicity to neuronal cells.

Conclusions:

  • Cyclodextrins can promote the toxic aggregation of Abeta.
  • Careful consideration is needed when using cyclodextrins for BBB delivery or treating brain disorders due to potential Abeta-induced toxicity.