SERCApumper

SERCApumper is a term used in biomedicine to describe a class of agents or engineered proteins designed to enhance the activity of SERCA pumps, the Ca2+-transporting enzymes of the sarco/endoplasmic reticulum. SERCA pumps move calcium from the cytosol into the SR or ER lumen using ATP hydrolysis, a process essential for muscle relaxation and calcium homeostasis in many cell types. SERCApumper agents aim to increase the rate or efficiency of this calcium sequestration, thereby lowering cytosolic Ca2+ transients after excitation and promoting faster relaxation or stabilizing intracellular calcium levels.

These agents may act by increasing pump turnover, stabilizing the pump in a high-activity conformation, or upregulating pump expression. They can be small molecules that directly activate SERCA, peptides that modulate regulatory proteins such as phospholamban, or gene therapies that raise SERCA2a expression in cardiac tissue. In preclinical studies, several SERCA activators have shown improved calcium handling and functional outcomes in models of heart disease and muscle disorders. In humans, research has included gene therapy approaches to augment SERCA2a, notably in cardiac failure trials, though results have been mixed and development continues.

Applications of SERCApumper strategies include potential treatments for heart failure, certain myopathies, and neurodegenerative disorders where calcium mishandling contributes to pathology. Challenges include achieving tissue specificity, avoiding calcium overload or depletion, and ensuring long-term safety.

See also: SERCA, Ca2+-ATPase, phospholamban, CUPID, calcium homeostasis.