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 (Ca<sup>2+</sup>) levels is a common occurrence in neurodegenerative diseases, including Alzheimer’s disease (AD), the study of proteins that can correct neuronal Ca<sup>2+</sup> dysregulation is of great interest. In previous work...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/11/6055 |
| _version_ | 1797531468131467264 |
|---|---|
| author | Maria Berrocal Lucia Saez Ana M. Mata |
| author_facet | Maria Berrocal Lucia Saez Ana M. Mata |
| author_sort | Maria Berrocal |
| collection | DOAJ |
| description | Since dysregulation of intracellular calcium (Ca<sup>2+</sup>) levels is a common occurrence in neurodegenerative diseases, including Alzheimer’s disease (AD), the study of proteins that can correct neuronal Ca<sup>2+</sup> dysregulation is of great interest. In previous work, we have shown that plasma membrane Ca<sup>2+</sup>-ATPase (PMCA), a high-affinity Ca<sup>2+</sup> pump, is functionally impaired in AD and is inhibited by amyloid-β peptide (Aβ) and tau, two key components of pathological AD hallmarks. On the other hand, sorcin is a Ca<sup>2+</sup>-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 Ca<sup>2+</sup>-ATPase (SERCA), and other modulators of intracellular Ca<sup>2+</sup> 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 Aβ and tau toxicity. Results show sorcin as an activator of PMCA, which also prevents the inhibitory effects of Aβ and tau on the pump, and counteracts the neurotoxicity of Aβ and tau by interacting with them. |
| first_indexed | 2024-03-10T10:44:14Z |
| format | Article |
| id | doaj.art-c2b669274d3a4755adec440b1c973063 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:44:14Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c2b669274d3a4755adec440b1c9730632023-11-21T22:44:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012211605510.3390/ijms22116055Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump ActivityMaria Berrocal0Lucia Saez1Ana M. Mata2Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias and Instituto de Biomarcadores de Patologías Moleculares, Universidad de Extremadura, 06006 Badajoz, SpainDepartamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias and Instituto de Biomarcadores de Patologías Moleculares, Universidad de Extremadura, 06006 Badajoz, SpainDepartamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias and Instituto de Biomarcadores de Patologías Moleculares, Universidad de Extremadura, 06006 Badajoz, SpainSince dysregulation of intracellular calcium (Ca<sup>2+</sup>) levels is a common occurrence in neurodegenerative diseases, including Alzheimer’s disease (AD), the study of proteins that can correct neuronal Ca<sup>2+</sup> dysregulation is of great interest. In previous work, we have shown that plasma membrane Ca<sup>2+</sup>-ATPase (PMCA), a high-affinity Ca<sup>2+</sup> pump, is functionally impaired in AD and is inhibited by amyloid-β peptide (Aβ) and tau, two key components of pathological AD hallmarks. On the other hand, sorcin is a Ca<sup>2+</sup>-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 Ca<sup>2+</sup>-ATPase (SERCA), and other modulators of intracellular Ca<sup>2+</sup> 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 Aβ and tau toxicity. Results show sorcin as an activator of PMCA, which also prevents the inhibitory effects of Aβ and tau on the pump, and counteracts the neurotoxicity of Aβ and tau by interacting with them.https://www.mdpi.com/1422-0067/22/11/6055sorcinplasma membrane Ca<sup>2+</sup>-ATPase (PMCA)amyloid-β peptidetaufunctional modulationneurodegeneration |
| spellingShingle | Maria Berrocal Lucia Saez Ana M. Mata Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump Activity International Journal of Molecular Sciences sorcin plasma membrane Ca<sup>2+</sup>-ATPase (PMCA) amyloid-β peptide tau functional modulation neurodegeneration |
| title | Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump Activity |
| title_full | Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump Activity |
| title_fullStr | Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump Activity |
| title_full_unstemmed | Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump Activity |
| title_short | Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump Activity |
| title_sort | sorcin activates the brain pmca and blocks the inhibitory effects of molecular markers of alzheimer s disease on the pump activity |
| topic | sorcin plasma membrane Ca<sup>2+</sup>-ATPase (PMCA) amyloid-β peptide tau functional modulation neurodegeneration |
| url | https://www.mdpi.com/1422-0067/22/11/6055 |
| work_keys_str_mv | AT mariaberrocal sorcinactivatesthebrainpmcaandblockstheinhibitoryeffectsofmolecularmarkersofalzheimersdiseaseonthepumpactivity AT luciasaez sorcinactivatesthebrainpmcaandblockstheinhibitoryeffectsofmolecularmarkersofalzheimersdiseaseonthepumpactivity AT anammata sorcinactivatesthebrainpmcaandblockstheinhibitoryeffectsofmolecularmarkersofalzheimersdiseaseonthepumpactivity |