Parkinson's disease (PD) is a neurodegenerative disorder characterized by the accumulation of a protein called α-synuclein (α-syn) into inclusions known as lewy bodies (LB) within neurons. This accumulation is also due to insufficient formation and activity of dopamine produced in certain neurons within the substantia nigra. Lewy bodies are the pathological hallmark of the idiopathic disorder and the cascade that allows α-synuclein to misfold, aggregate and form these inclusions has been the subject of intensive research. Targeting these early steps of oligomerization is one of the main therapeutic approaches in order to develop neurodegenerative-modifying agents. Because the folding and refolding of alpha synuclein is the key point of this cascade, we are interested in this review to summarize the role of some molecular chaperones proteins such as Hsp70, Hsp90 and small heat shock proteins (sHsp) and Hsp 104. Hsp70 and its co-chaperone, Hsp70 and small heat shock proteins can prevent neurodegeneration by preventing α-syn misfolding, oligomerization and aggregation in vitro and in Parkinson disease animal models. Hsp104 is able to resolve disordered protein aggregates and cross beta amyloid conformers. Together, these chaperones have a complementary effect and can be a target for therapeutic intervention in PD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijbiomac.2013.05.032 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Assessment of Hsp90β-selective inhibitor safety and on-target effects.
Sci Rep
January 2025
Department of Chemistry and Biochemistry, The University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
The heat shock protein 90 (Hsp90) family of molecular chaperones mediates the folding and activation of ~ 400 client proteins, many of which contribute to oncogenesis. As a result, Hsp90 pan-inhibitors, which inhibit all four Hsp90 isoforms, have been investigated in the clinic for the treatment of cancer. Unfortunately, detrimental side effects were observed and hindered the clinical development of pan-Hsp90 inhibitors.
View Article and Find Full Text PDFA conserved chaperone protein is required for the formation of a non-canonical type VI secretion system spike tip complex.
J Biol Chem
January 2025
Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1; Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8S 4K1. Electronic address:
Type VI secretion systems (T6SS) are dynamic protein nanomachines found in Gram-negative bacteria that deliver toxic effector proteins into target cells in a contact-dependent manner. Prior to secretion, many T6SS effector proteins require chaperones and/or accessory proteins for proper loading onto the structural components of the T6SS apparatus. However, despite their established importance, the precise molecular function of several T6SS accessory protein families remains unclear.
View Article and Find Full Text PDFHsp90, DnaK, and ClpB collaborate in protein reactivation.
Proc Natl Acad Sci U S A
February 2025
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892.
Hsp70, Hsp90, and ClpB/Hsp100 are molecular chaperones that help regulate proteostasis. Bacterial and yeast Hsp70s and their cochaperones function synergistically with Hsp90s to reactivate inactive and aggregated proteins by a mechanism that requires a direct interaction between Hsp90 and Hsp70 both in vitro and in vivo. and yeast Hsp70s also collaborate in bichaperone systems with ClpB and Hsp104, respectively, to disaggregate and reactivate aggregated proteins and amyloids such as prions.
View Article and Find Full Text PDFMechanism of chaperone recruitment and retention on mitochondrial precursors.
Mol Biol Cell
January 2025
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Nearly all mitochondrial proteins are imported into mitochondria from the cytosol. How nascent mitochondrial precursors acquire and sustain import-competence in the cytosol under normal and stress conditions is incompletely understood. Here, we show that under normal conditions, the Hsc70 and Hsp90 systems interact with and redundantly minimize precursor degradation.
View Article and Find Full Text PDFStructural analysis of extracellular ATP-independent chaperones of streptococcal species and protein substrate interactions.
mSphere
January 2025
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Unlabelled: During infection, bacterial pathogens rely on secreted virulence factors to manipulate the host cell. However, in gram-positive bacteria, the molecular mechanisms underlying the folding and activity of these virulence factors after membrane translocation are not clear. Here, we solved the protein structures of two secreted parvulin and two secreted cyclophilin-like peptidyl-prolyl isomerase (PPIase) ATP-independent chaperones found in gram-positive streptococcal species.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!