Protein homeostasis as a therapeutic target for diseases of protein conformation

Area of Science:

• Molecular Biology
• Cellular Biology
• Pharmacology

Background:

• Protein misfolding and aggregation are linked to numerous human diseases, creating a need for novel therapeutic targets.
• The proteostasis network (PN) maintains proteome stability through stress signaling, molecular chaperones, and clearance systems.
• Aging, stress, and disease can impair PN function, leading to protein conformational diseases.

Purpose of the Study:

• To investigate small molecules that can enhance the proteostasis network (PN) capacity.
• To assess the potential of activating cellular stress responses and clearance mechanisms as a therapeutic strategy.
• To protect cellular proteostasis against proteotoxicity and prevent damage in protein conformational diseases.

Main Methods:

• Assessment of small molecules that activate the heat shock response.
• Evaluation of compounds that stimulate the unfolded protein response.
• Analysis of agents that enhance protein clearance mechanisms.

Main Results:

• Small molecules can activate key cellular stress pathways, including the heat shock and unfolded protein responses.
• Enhanced chaperone activity and clearance mechanisms increase the cell's capacity to manage proteotoxicity.
• This strategy establishes a cytoprotective state against protein misfolding and aggregation.

Conclusions:

• Enhancing the proteostasis network through small molecules is a viable therapeutic approach.
• Activating cell stress pathways and chaperone activity offers protection against protein conformational diseases.
• This strategy represents a promising avenue for preventing cellular damage in diseases associated with protein misfolding.