Chaperone proteins protect against desmin fragment amyloid aggregation

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Protein Misfolding Diseases

Background:

• Desmin-related cardiomyopathy involves desmin cleavage and aggregation.
• Misfolded desmin fragments are amyloidogenic, promoting further aggregation.
• AlphaB-crystallin and HSP27 are cardioprotective chaperones overexpressed during cellular stress.

Purpose of the Study:

• To investigate the effect of alphaB-crystallin and HSP27 on desmin fragment amyloid formation.
• To analyze changes in secondary structure, kinetics, and morphology during amyloidogenesis.
• To compare the chaperone activity of alphaB-crystallin and HSP27 against desmin fragment amyloid.

Main Methods:

• Studied secondary structure changes, kinetics, and morphology of desmin fragment amyloid formation.
• Assessed amyloid formation with and without varying concentrations of alphaB-crystallin and HSP27.
• Performed interaction studies to determine binding sites and mechanisms.

Main Results:

• Both alphaB-crystallin and HSP27 prevented or delayed desmin fragment amyloid formation in a concentration-dependent manner.
• No amyloid disaggregation was observed.
• AlphaB-crystallin exhibited superior chaperone activity compared to HSP27, correlating with increased binding sites.
• Chaperones reversibly captured monomers/oligomers and irreversibly capped amyloid fibrils.

Conclusions:

• AlphaB-crystallin and HSP27 effectively inhibit desmin fragment amyloid formation by interacting with both monomeric and fibrillar forms.
• These chaperones recognize distinct binding sites on desmin fragments and amyloid fibrils.
• The findings highlight the potential of these chaperones in mitigating desmin-related cardiomyopathy progression.