Ubiquitin-proteasome system alterations in a striatal cell model of huntington's disease

2007 ◽  
Vol 85 (8) ◽  
pp. 1774-1788 ◽  
Author(s):  
Jesse M. Hunter ◽  
Mathieu Lesort ◽  
Gail V.W. Johnson
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cell Model ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome

scholarly journals Blocking acid-sensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasome system-dependent mechanism

2008 ◽  
Vol 17 (20) ◽  
pp. 3223-3235 ◽  
Author(s):  
Hon Kit Wong ◽  
Peter O. Bauer ◽  
Masaru Kurosawa ◽  
Anand Goswami ◽  
Chika Washizu ◽  
...  
Keyword(s):  
Ion Channel ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome ◽  
Dependent Mechanism

scholarly journals Impaired ubiquitin–proteasome system activity in the synapses of Huntington's disease mice

2008 ◽  
Vol 180 (6) ◽  
pp. 1177-1189 ◽  
Author(s):  
Jianjun Wang ◽  
Chuan-En Wang ◽  
Adam Orr ◽  
Suzanne Tydlacka ◽  
Shi-Hua Li ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Ubiquitin Proteasome System ◽  
Synaptic Function ◽  
Fluorescent Reporters ◽  
Biochemical Assays ◽  
Neuronal Processes ◽  
Ubiquitin Proteasome ◽  
And Function ◽  
Other Neurological Disease

Huntington's disease (HD) is caused by the expansion of a polyglutamine tract in the N-terminal region of huntingtin (htt) and is characterized by selective neurodegeneration. In addition to forming nuclear aggregates, mutant htt accumulates in neuronal processes as well as synapses and affects synaptic function. However, the mechanism for the synaptic toxicity of mutant htt remains to be investigated. We targeted fluorescent reporters for the ubiquitin–proteasome system (UPS) to presynaptic or postsynaptic terminals of neurons. Using these reporters and biochemical assays of isolated synaptosomes, we found that mutant htt decreases synaptic UPS activity in cultured neurons and in HD mouse brains that express N-terminal or full-length mutant htt. Given that the UPS is a key regulator of synaptic plasticity and function, our findings offer insight into the selective neuronal dysfunction seen in HD and also establish a method to measure synaptic UPS activity in other neurological disease models.

scholarly journals The JAK2-STAT3 pathway controls a beneficial proteostasis response of reactive astrocytes in Huntington’s disease

2021 ◽  
Author(s):  
L. Abjean ◽  
L. Ben Haim ◽  
M. Riquelme-Perez ◽  
P. Gipchtein ◽  
C. Derbois ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Ubiquitin Proteasome System ◽  
Reactive Astrocytes ◽  
Stat3 Pathway ◽  
Functional Changes ◽  
Ubiquitin Proteasome ◽  
Open Question ◽  
Proteolytic Capacity

AbstractHuntington’s disease (HD) is a fatal neurodegenerative disease characterized by striatal neurodegeneration, aggregation of mutant Huntingtin (mHTT) and the presence of reactive astrocytes. Astrocytes are important partners for neurons and engage in a specific reactive response in HD that involves morphological, molecular and functional changes. How reactive astrocytes contribute to HD is still an open question, especially because their reactive state is poorly reproduced in mouse models.Here, we show that the JAK2-STAT3 pathway, a central cascade controlling the reactive response of astrocytes, is activated in the putamen of HD patients. Selective activation of this cascade in astrocytes reduces the number and size of neuronal mHTT aggregates and improves neuronal features in two HD mouse models. Moreover, activation of the JAK2-STAT3 pathway in astrocytes coordinates a transcriptional program that increases their intrinsic proteolytic capacity, through the lysosomes and the ubiquitin-proteasome system, and enhances their production of the co-chaperone DNAJB1, which is released in exosomes.Together, our results show that the JAK2-STAT3 pathway controls a beneficial proteostasis response in reactive astrocytes in HD, which involves bi-directional signalling with neurons to reduce mHTT aggregation and toxicity.

The Ubiquitin-Proteasome System in Huntington’s Disease

2005 ◽  
Vol 11 (6) ◽  
pp. 583-594 ◽  
Author(s):  
A. G. Valera ◽  
M. Díaz-Hernández ◽  
F. HernÁNdez ◽  
Z. Ortega ◽  
J. J. Lucas
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome
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