Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer's Disease on the Pump Activity

Since dysregulation of intracellular calcium (Ca2+) levels is a common occurrence in neurodegenerative diseases, including Alzheimer's disease (AD), the study of proteins that can correct neuronal Ca2+ dysregulation is of great interest. In previous work, we have shown that plasma membrane Ca2+-ATPase (PMCA), a high-affinity Ca2+ pump, is functionally impaired in AD and is inhibited by amyloid-beta peptide (A beta) and tau, two key components of pathological AD hallmarks. On the other hand, sorcin is a Ca2+-binding protein highly expressed in the brain, although its mechanism of action is far from being clear. Sorcin has been shown to interact with the intracellular sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), and other modulators of intracellular Ca2+ signaling, such as the ryanodine receptor or presenilin 2, which is closely associated with AD. The present work focuses on sorcin in search of new regulators of PMCA and antagonists of A beta and tau toxicity. Results show sorcin as an activator of PMCA, which also prevents the inhibitory effects of A beta and tau on the pump, and counteracts the neurotoxicity of A beta and tau by interacting with them.

Automated summary

The study focuses on sorcin as a potential regulator of PMCA and an antagonist of A beta and tau toxicity. Results demonstrate that sorcin acts as an activator of PMCA, counteracting the inhibitory effects of A beta and tau on the pump, and interacting with them to neutralize their neurotoxicity.