Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Transthyretin amyloidoses are progressive disorders caused by toxic transthyretin aggregate accumulation, often affecting the peripheral nervous system.
• Current therapies face challenges due to disease complexity, highlighting the need for multi-target approaches.

Purpose of the Study:

• To evaluate the protective effects of curcumin on transthyretin-induced cytotoxicity.
• To investigate curcumin's impact on transthyretin aggregate deposition and clearance in vivo and in vitro.

Main Methods:

• In vitro assessment of curcumin's effect on caspase-3 activity and endoplasmic reticulum stress markers.
• Administration of curcumin to a mouse model of Familial Amyloidotic Polyneuropathy (FAP).
• Analysis of curcumin's impact on transthyretin aggregate deposition, tissue remodeling, and macrophage-mediated clearance in FAP mice.

Main Results:

• Curcumin reduced cytotoxicity induced by transthyretin oligomers in vitro.
• In FAP mice, curcumin decreased transthyretin aggregate deposition and toxicity in the gastrointestinal tract and dorsal root ganglia.
• Curcumin remodeled amyloid material and enhanced the clearance of transthyretin oligomers by macrophages.

Conclusions:

• Curcumin demonstrates protective effects against transthyretin amyloidosis.
• Curcumin acts as a multi-target agent, addressing both aggregate toxicity and clearance mechanisms.
• Curcumin and its derivatives are promising disease-modifying agents for late-stage transthyretin amyloidosis.