Prions, Proteasomes, and Mad Cows
All cells have the capacity to selectively degrade misfolded intracellular proteins, which, if they accumulated, could interfere with normal function and could be toxic. Such proteins may arise by mutation, errors in gene expression, failure to fold correctly, spontaneous denaturation, or postsynthetic damage (for example, by oxygen radicals). How often such events occur in cells is uncertain, largely because the ubiquitin–proteasome pathway rapidly degrades such aberrant proteins, including those that cause various inherited diseases, such as cystic fibrosis and certain hemoglobinopathies. This pathway also protects against neurodegenerative diseases. Direct evidence that the abnormal toxic proteins in these various diseases can inhibit the functioning of the proteasome pathway has been lacking. Recently, Kristiansen et al presented strong evidence that soluble aggregates of the toxic protein may cause prion disease by specifically inhibiting the function of the 26S proteasome. A major gap in our understanding has been how the conversion of PrPC to PrPSc eventually kills neurons. Kristiansen et al showed that neurons and neuroblastoma cells infected with prions have reduced proteasomal activity against model substrates. Loss of proteasomal function affects many critical cellular processes and can induce apoptosis.
On Prions, Proteasomes, and Mad Cows
NEJM 2007 357:1150-1152
A good insight into the ubiquitin-proteasome pathway, for deleting misfolded prion proteins into the ‘recycle bin’.
[...] Prions, Proteasomes, and Mad Cows [...]
[...] Prions, Proteasomes, and Mad Cows [...]
I was looking for ubiquitin protein information and saw this. thanks for the info! you may also like the ubiquitin webinar that science magazine is putting on: The Ubiquitin-Proteasome Pathway
[...] Prions, Proteasomes, and Mad Cows [...]