- Dynein—Mutations Put the Brakes on Aggregate Clearance
To ask if dynein was involved in the clearance of toxic proteins, co-first authors Brinda Ravikumar and Abraham Acevedo-Arozena first looked at the turnover of huntingtin and α-synuclein in cells Using cells with inducible expression of a GFP-huntingtin fusion containing 74 Q repeats, or an A53T synuclein mutant, allowed the researchers to switch on protein production, then turn it off and
- Protein-Protein Interactions, Cytoskeleton Implicated in . . . - ALZFORUM
Meanwhile researchers in Paul Patterson's lab at the California Institute of Technology in Pasadena have used a different approach to probe huntingtin's role in the disease They expressed, inside cultured cells, monoclonal antibodies raised against various epitopes of huntingtin to perturb its protein-protein interactions Their results, published online on January 15 in PNAS, reveal two
- Broad Screens Yield Pathologic Pathways for Huntington’s, SMA
In so doing, huntingtin would cause the release of calcium from the ER This would then activate the SOC pathway, flooding the cytoplasm with even more calcium “You basically have continuous influx of calcium into the cell, which creates continuous calcium stress,” he said
- Polyglutamine, Inclusion Bodies and the Proteasome—The . . . - ALZFORUM
To measure activity of the ubiquitin proteasome system (UPS), both groups used a similar strategy—a degradable green fluorescent protein (GFP) chimera easily quantified by fluorescence microscopy Put this chimera into a cell along with fodder for inclusion bodies, say, a polyglutamine protein such as huntingtin or SCA7, and you have the makings of a system that reveals how inclusion
- New Targets for Neurodegenerative Diseases: Autophagy and More
Two papers this week feature inventive strategies for uncovering new targets and potential therapies to treat neurodegenerative disease Both deal directly with Huntington disease, and particularly with the polyglutamine-expanded huntingtin protein, but at the same time they present possible
- Society for Neuroscience Annual Meeting 2009 - ALZFORUM
Huntingtin: It’s the Ps, Not the Qs Morfini and colleagues previously showed that poly-glutamine expanded huntingtin, as well, interferes with anterograde transport: It activates cJun N-terminal kinase 3 (JNK3) to phosphorylate kinesin, uncoupling the motor from its tracks (see ARF related news story on Morfini et al , 2009)
- BIIB080 - ALZFORUM
Previous ASO therapies—developed by IONIS against mutant SMA, SOD1, and huntingtin proteins—are delivered intrathecally to patients The SMA, SOD1, and this tau-targeted ASO are partnered with Biogen; the ASO targeting huntingtin is partnered with Roche
- Cell-Type-Specific RNA Analysis Probes Selective Vulnerability in . . .
How does mutant huntingtin protein cause striatal neurons to die? On July 17 in Neuron online, researchers led by Myriam Heiman at the Massachusetts Institute of Technology suggest that an early insult to mitochondria could kick off inflammation and neurodegeneration Using multiple overlapping
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