Protein turnover and inclusion body formation.
In a recent study, we investigated the relationship between inclusion body (IB) formation and the activity of the ubiquitin-proteasome system (UPS) in a primary neuron model of Huntington disease. We followed individual neurons over the course of days and monitored the level of mutant huntingtin (htt) (which causes Huntington disease), IB formation, UPS function, and neuronal toxicity. The accumulation of UPS substrates and neuronal toxicity increased with increasing levels of proteasome inhibition. The UPS was more impaired in neurons that subsequently formed IBs than in those that did not; however, after IBs formed, UPS function improved. These findings suggest that IB formation is a protective cellular response mediated in part by increased degradation of intracellular protein.
Mitra
Siddhartha
S
Gladstone Institute of Neurological Disease, San Francisco, CA 945158, USA.
Tsvetkov
Andrey S
AS
Finkbeiner
Steven
S
D001343:Autophagy / Q000502:physiology; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002479:Inclusion Bodies / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex