Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/ijms22116055
Keywords
sorcin; plasma membrane Ca2+-ATPase (PMCA); amyloid-beta peptide; tau; functional modulation; neurodegeneration
Funding
- Spanish Ministerio de Economia y Competitividad [BFU2017-85723-P]
- Junta de Extremadura [GR18118]
- grant for the promotion of youth employment and implementation of the Youth Guarantee in I + D + I 2018 [PEJ2018-003710-P]
- European Union (Fondo Europeo de Desarrollo Regional)
- European Union (FEDER)
- European Union (Fondo Social Europeo, FSE)
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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.
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.
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