Pathophysiological Role of Transient Receptor Potential Mucolipin Channel 1 in Calcium-Mediated Stress-Induced Neurodegenerative Diseases
Mucolipins (TRPML) are endosome/lysosome Ca2+ permeable channels belonging to the family of transient receptor potential channels. In mammals, there are three TRPML proteins, TRPML1, 2, and 3, encoded by MCOLN1-3 genes. Among these channels, TRPML1 is a reactive oxygen species sensor localized on th...
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2020.00251/full |
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| author | Giorgio Santoni Federica Maggi Federica Maggi Consuelo Amantini Oliviero Marinelli Oliviero Marinelli Massimo Nabissi Maria Beatrice Morelli Maria Beatrice Morelli |
| author_facet | Giorgio Santoni Federica Maggi Federica Maggi Consuelo Amantini Oliviero Marinelli Oliviero Marinelli Massimo Nabissi Maria Beatrice Morelli Maria Beatrice Morelli |
| author_sort | Giorgio Santoni |
| collection | DOAJ |
| description | Mucolipins (TRPML) are endosome/lysosome Ca2+ permeable channels belonging to the family of transient receptor potential channels. In mammals, there are three TRPML proteins, TRPML1, 2, and 3, encoded by MCOLN1-3 genes. Among these channels, TRPML1 is a reactive oxygen species sensor localized on the lysosomal membrane that is able to control intracellular oxidative stress due to the activation of the autophagic process. Moreover, genetic or pharmacological inhibition of the TRPML1 channel stimulates oxidative stress signaling pathways. Experimental data suggest that elevated levels of reactive species play a role in several neurological disorders. There is a need to gain better understanding of the molecular mechanisms behind these neurodegenerative diseases, considering that the main sources of free radicals are mitochondria, that mitochondria/endoplasmic reticulum and lysosomes are coupled, and that growing evidence links neurodegenerative diseases to the gain or loss of function of proteins related to lysosome homeostasis. This review examines the significant roles played by the TRPML1 channel in the alterations of calcium signaling responsible for stress-mediated neurodegenerative disorders and its potential as a new therapeutic target for ameliorating neurodegeneration in our ever-aging population. |
| first_indexed | 2024-12-21T15:12:05Z |
| format | Article |
| id | doaj.art-6d2f541ab2e145e1852103bf3f833eb2 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-21T15:12:05Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-6d2f541ab2e145e1852103bf3f833eb22022-12-21T18:59:15ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-03-011110.3389/fphys.2020.00251522417Pathophysiological Role of Transient Receptor Potential Mucolipin Channel 1 in Calcium-Mediated Stress-Induced Neurodegenerative DiseasesGiorgio Santoni0Federica Maggi1Federica Maggi2Consuelo Amantini3Oliviero Marinelli4Oliviero Marinelli5Massimo Nabissi6Maria Beatrice Morelli7Maria Beatrice Morelli8Immunopathology Laboratory, School of Pharmacy, University of Camerino, Camerino, ItalyImmunopathology Laboratory, School of Pharmacy, University of Camerino, Camerino, ItalyDepartment of Molecular Medicine, Sapienza University, Rome, ItalyImmunopathology Laboratory, School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, ItalyImmunopathology Laboratory, School of Pharmacy, University of Camerino, Camerino, ItalyImmunopathology Laboratory, School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, ItalyImmunopathology Laboratory, School of Pharmacy, University of Camerino, Camerino, ItalyImmunopathology Laboratory, School of Pharmacy, University of Camerino, Camerino, ItalyImmunopathology Laboratory, School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, ItalyMucolipins (TRPML) are endosome/lysosome Ca2+ permeable channels belonging to the family of transient receptor potential channels. In mammals, there are three TRPML proteins, TRPML1, 2, and 3, encoded by MCOLN1-3 genes. Among these channels, TRPML1 is a reactive oxygen species sensor localized on the lysosomal membrane that is able to control intracellular oxidative stress due to the activation of the autophagic process. Moreover, genetic or pharmacological inhibition of the TRPML1 channel stimulates oxidative stress signaling pathways. Experimental data suggest that elevated levels of reactive species play a role in several neurological disorders. There is a need to gain better understanding of the molecular mechanisms behind these neurodegenerative diseases, considering that the main sources of free radicals are mitochondria, that mitochondria/endoplasmic reticulum and lysosomes are coupled, and that growing evidence links neurodegenerative diseases to the gain or loss of function of proteins related to lysosome homeostasis. This review examines the significant roles played by the TRPML1 channel in the alterations of calcium signaling responsible for stress-mediated neurodegenerative disorders and its potential as a new therapeutic target for ameliorating neurodegeneration in our ever-aging population.https://www.frontiersin.org/article/10.3389/fphys.2020.00251/fullneurodegenerative diseaseTRPML1lysosomal storage diseaseoxidative stressmitochondriaautophagy |
| spellingShingle | Giorgio Santoni Federica Maggi Federica Maggi Consuelo Amantini Oliviero Marinelli Oliviero Marinelli Massimo Nabissi Maria Beatrice Morelli Maria Beatrice Morelli Pathophysiological Role of Transient Receptor Potential Mucolipin Channel 1 in Calcium-Mediated Stress-Induced Neurodegenerative Diseases Frontiers in Physiology neurodegenerative disease TRPML1 lysosomal storage disease oxidative stress mitochondria autophagy |
| title | Pathophysiological Role of Transient Receptor Potential Mucolipin Channel 1 in Calcium-Mediated Stress-Induced Neurodegenerative Diseases |
| title_full | Pathophysiological Role of Transient Receptor Potential Mucolipin Channel 1 in Calcium-Mediated Stress-Induced Neurodegenerative Diseases |
| title_fullStr | Pathophysiological Role of Transient Receptor Potential Mucolipin Channel 1 in Calcium-Mediated Stress-Induced Neurodegenerative Diseases |
| title_full_unstemmed | Pathophysiological Role of Transient Receptor Potential Mucolipin Channel 1 in Calcium-Mediated Stress-Induced Neurodegenerative Diseases |
| title_short | Pathophysiological Role of Transient Receptor Potential Mucolipin Channel 1 in Calcium-Mediated Stress-Induced Neurodegenerative Diseases |
| title_sort | pathophysiological role of transient receptor potential mucolipin channel 1 in calcium mediated stress induced neurodegenerative diseases |
| topic | neurodegenerative disease TRPML1 lysosomal storage disease oxidative stress mitochondria autophagy |
| url | https://www.frontiersin.org/article/10.3389/fphys.2020.00251/full |
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