Neurophilosophy

Alzheimers_amyloid_beta_fibril_small.jpg

This three-dimensional reconstruction of an amyloid fibril (found at Discover) was created by Nikolaus Grigorieff and his colleagues at Brandeis University, by computer processing of a transmission electron cryomicroscopy image. It is the most detailed image yet of the abnormally folded protein which accumulates to form the senile plaques that are a pathological hallmark of Alzheimer’s Disease.

The fibrils consist of a protein fragment called amyloid-beta 1-40, an insoluble forty amino acid polypeptide generated by the sequential actions of a number of enzymes on the amyloid precursor protein (APP). These fragments polymerize (or join end-to-end) and are deposited in the spaces around neurons; the deposits (plaques) are toxic, and are widely believed to be responsible for the loss of cells that occurs in Alzheimer’s. However, this has not yet been determined – the plaques could be an effect, rather than the cause, of neurodegeneration.

The exact mechanism by which plaque deposition occurs is also unclear, but several cellular processes are now implicated. Recent research suggests that fibrils are formed by a seeding mechanism like the one proposed for the aggregation of prion protein in the transmissible spongiform encephalopathies; that amyloid-beta folds abnormally because of defects in the function of molecular chaperones, which facilitate the proper folding of proteins; and that plaque formation occurs because of cells’ inability to destroy incorrectly folded proteins.

Detailed structural analyses such as this one should therefore help researchers to elucidate the mechanisms of amyloid fibril formation and senile plaque deposition. Such studies should also provide some insight into other neurodegenerative diseases, because the aggregation of abnormally folded proteins is a characteristic feature of all such conditions.

Comments

  1. #1 Karyn Romeis
    July 16, 2008

    Something so devastating has no business looking so beautiful!

  2. #2 saij
    July 16, 2008

    It looks like an evil (cylon?) manta ray.

  3. #3 Jon h
    July 16, 2008

    It would be nice if it wasn’t colored to look eeeeevil, so you could actually see the details.

  4. #4 Karyn Romeis
    July 17, 2008

    How odd. I didn’t see those colours as evil at all. To me they look like fire, or late sunset – not evil at all, but ethereally beautiful. How differently we perceive things.

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