25 May 2001. Aggregates of proteins are a common feature in many
neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's,
fronto-temporal dementia and ALS. Their role in contributing to these
diseases remains unclear. Normally, cells dispose of the unwanted
protein clumps by tagging them with ubiquitin, which then are destroyed
by a complex called the proteasome. In today's Science, Neil Bence and
colleagues report that once the aggregates are formed, the aggregates
themselves seem to almost completely block the ubiquitin-proteasome
system from working. They showed this to be the case with two different
proteins, the pathogenic form of huntingtin and a folding mutant of
cystic fibrosis transmembrane conductance regulator. The authors write:
"Because of the central role of ubiquitin-dependent proteolysis in
regulating fundamental events such as cell division and apoptosis, our
data suggest a potential mechanism linking proein aggregation to
cellular disregulation and cell death." The relevance of this mechanism
to Alzheimer's disease may be disputed. Unlike aggregating proteins in
other major neurodegenerative diseases, A-beta aggregates (a hallmark of
Alzheimer's disease) are largely found outside the cell. However, some
researchers suggest that Aβ also aggregates within the neuron.
Reference:Bence NF, Sampat RM, Kopito RR. Related Articles, Links. Impairment of the ubiquitin-proteasome system by protein aggregation. Science. 2001 May 25;292(5521):1552-5. Abstract
See related story from Science Daily
|
Home
Impairment of the ubiquitin-proteasome system by protein aggregation.
