In:
eLife, eLife Sciences Publications, Ltd, Vol. 4 ( 2015-02-05)
Abstract:
Prion proteins are anchored to the surface of brain cells called neurons. Normally, prion proteins are folded into a specific three-dimensional shape that enables them to carry out their normal roles in the brain. However, they can be misfolded into a different shape known as PrPSc, which can cause Creutzfeldt-Jakob disease and other serious conditions that affect brain function and ultimately lead to death. The PrPSc proteins can force normal prion proteins to change into the PrPSc form, so that over time this form accumulates in the brain. They are essential components of infectious particles termed ‘prions’ and this is why prion diseases are infectious: if prions from one individual enter the brain of another individual they can cause disease in the recipient. The UK outbreak of variant Creutzfeldt-Jakob disease in humans in the 1990s is thought to be due to the consumption of meat from cattle with a prion disease known as mad cow disease. An enzyme called ADAM10 can cut normal prion proteins from the surface of neurons. However, it is not clear whether ADAM10 can also target the PrPSc proteins and what impact this may have on the development of prion diseases. Here, Altmeppen et al. studied mutant mice that were missing ADAM10 in neurons in the front portion of their brain. These mice had a higher number of normal prion proteins on the surface of their neurons than normal mice did. When mice missing ADAM10 were infected with prions, more PrPSc accumulated in their brain and disease symptoms developed sooner than when normal mice were infected. This supports the view that mice with higher numbers of prion proteins are more vulnerable to prion disease. However, disease symptoms did not spread as quickly to other parts of the brain in the mice missing ADAM10. This suggests that by releasing prion proteins from the surface of neurons, ADAM10 helps PrPSc proteins to spread around the brain. Recently, it has been suggested that prion proteins may also play a role in Alzheimer's disease and other neurodegenerative conditions. Therefore, Altmeppen et al.'s findings may help to develop new therapies for other forms of dementia. The next challenge is to understand the precise details of how ADAM10 works.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.04260.001
DOI:
10.7554/eLife.04260.002
DOI:
10.7554/eLife.04260.003
DOI:
10.7554/eLife.04260.004
DOI:
10.7554/eLife.04260.005
DOI:
10.7554/eLife.04260.006
DOI:
10.7554/eLife.04260.007
DOI:
10.7554/eLife.04260.008
DOI:
10.7554/eLife.04260.009
DOI:
10.7554/eLife.04260.010
DOI:
10.7554/eLife.04260.011
DOI:
10.7554/eLife.04260.012
DOI:
10.7554/eLife.04260.013
DOI:
10.7554/eLife.04260.014
DOI:
10.7554/eLife.04260.015
DOI:
10.7554/eLife.04260.016
DOI:
10.7554/eLife.04260.017
DOI:
10.7554/eLife.04260.018
DOI:
10.7554/eLife.04260.019
DOI:
10.7554/eLife.04260.020
DOI:
10.7554/eLife.04260.021
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2015
detail.hit.zdb_id:
2687154-3
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