Related Experiment Video
Updated: Jul 5, 2026
08:24
A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
Published on: November 25, 2022
CHIP targets toxic alpha-Synuclein oligomers for degradation
Julie E Tetzlaff1, Preeti Putcha, Tiago F Outeiro
1Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 02129, USA.
The Journal of Biological Chemistry
|April 26, 2008
Summary
Carboxyl terminus of Hsp70-interacting protein (CHIP) reduces toxic alpha-Synuclein (alphaSyn) oligomerization and degradation. CHIP targets toxic oligomeric alphaSyn species, offering potential Parkinson disease therapeutic strategies.
Area of Science:
- Neuroscience
- Molecular Biology
- Protein Biochemistry
Background:
- Alpha-Synuclein (alphaSyn) aggregation into oligomers, fibrils, and Lewy bodies is central to Parkinson disease pathogenesis.
- Oligomeric alphaSyn intermediates are hypothesized to be the most toxic species.
Purpose of the Study:
- To investigate the effect of the molecular chaperone CHIP on alphaSyn oligomerization and toxicity.
- To determine the domains of CHIP responsible for its effects on alphaSyn.
Main Methods:
- Utilized a novel bimolecular fluorescence complementation assay to study alphaSyn oligomerization.
- Investigated the role of CHIP's tetratricopeptide/Hsp70 binding domain and U-box/ubiquitin ligase domain.
Main Results:
- CHIP co-expression selectively reduced alphaSyn oligomerization and toxicity.
- CHIP's effect was dependent on its tetratricopeptide domain and independent of its U-box domain.
- CHIP specifically degraded toxic alphaSyn oligomers.
Conclusions:
- CHIP preferentially recognizes and mediates the degradation of toxic, oligomeric forms of alphaSyn.
- Understanding CHIP's mechanism may lead to drug therapies targeting oligomeric alphaSyn for Parkinson disease.
More Related Videos
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:13The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...