Emerging Role of DREAM in Healthy Brain and Neurological Diseases
The downstream regulatory element antagonist modulator (DREAM) is a multifunctional Ca -sensitive protein exerting a dual mechanism of action to regulate several Ca -dependent processes. Upon sumoylation, DREAM enters in nucleus where it downregulates the expression of several genes provided with a...
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| Veröffentlicht in: | International journal of molecular sciences 2023-05, Vol.24 (11), p.9177 |
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| creator | Molinaro, Pasquale Sanguigno, Luca Casamassa, Antonella Valsecchi, Valeria Sirabella, Rossana Pignataro, Giuseppe Annunziato, Lucio Formisano, Luigi |
| description | The downstream regulatory element antagonist modulator (DREAM) is a multifunctional Ca
-sensitive protein exerting a dual mechanism of action to regulate several Ca
-dependent processes. Upon sumoylation, DREAM enters in nucleus where it downregulates the expression of several genes provided with a consensus sequence named dream regulatory element (DRE). On the other hand, DREAM could also directly modulate the activity or the localization of several cytosolic and plasma membrane proteins. In this review, we summarize recent advances in the knowledge of DREAM dysregulation and DREAM-dependent epigenetic remodeling as a central mechanism in the progression of several diseases affecting central nervous system, including stroke, Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and neuropathic pain. Interestingly, DREAM seems to exert a common detrimental role in these diseases by inhibiting the transcription of several neuroprotective genes, including the sodium/calcium exchanger isoform 3 (NCX3), brain-derived neurotrophic factor (BDNF), pro-dynorphin, and c-fos. These findings lead to the concept that DREAM might represent a pharmacological target to ameliorate symptoms and reduce neurodegenerative processes in several pathological conditions affecting central nervous system. |
| doi_str_mv | 10.3390/ijms24119177 |
| format | Article |
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-sensitive protein exerting a dual mechanism of action to regulate several Ca
-dependent processes. Upon sumoylation, DREAM enters in nucleus where it downregulates the expression of several genes provided with a consensus sequence named dream regulatory element (DRE). On the other hand, DREAM could also directly modulate the activity or the localization of several cytosolic and plasma membrane proteins. In this review, we summarize recent advances in the knowledge of DREAM dysregulation and DREAM-dependent epigenetic remodeling as a central mechanism in the progression of several diseases affecting central nervous system, including stroke, Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and neuropathic pain. Interestingly, DREAM seems to exert a common detrimental role in these diseases by inhibiting the transcription of several neuroprotective genes, including the sodium/calcium exchanger isoform 3 (NCX3), brain-derived neurotrophic factor (BDNF), pro-dynorphin, and c-fos. These findings lead to the concept that DREAM might represent a pharmacological target to ameliorate symptoms and reduce neurodegenerative processes in several pathological conditions affecting central nervous system.</description><subject>Amyotrophic lateral sclerosis</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Brain-derived neurotrophic factor</subject><subject>c-Fos protein</subject><subject>Calcium</subject><subject>Calcium ions</subject><subject>Cell Nucleus - metabolism</subject><subject>Central nervous system</subject><subject>Conserved sequence</subject><subject>Development and progression</subject><subject>Dynorphin</subject><subject>Dynorphins - metabolism</subject><subject>Enzymes</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic transcription</subject><subject>Homeostasis</subject><subject>Kinases</subject><subject>Kv Channel-Interacting Proteins - 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metabolism</topic><topic>Brain-derived neurotrophic factor</topic><topic>c-Fos protein</topic><topic>Calcium</topic><topic>Calcium ions</topic><topic>Cell Nucleus - metabolism</topic><topic>Central nervous system</topic><topic>Conserved sequence</topic><topic>Development and progression</topic><topic>Dynorphin</topic><topic>Dynorphins - metabolism</topic><topic>Enzymes</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic transcription</topic><topic>Homeostasis</topic><topic>Kinases</topic><topic>Kv Channel-Interacting Proteins - metabolism</topic><topic>Ligands</topic><topic>Localization</topic><topic>Membrane proteins</topic><topic>Na+/Ca2+ exchanger</topic><topic>Nervous system diseases</topic><topic>Neurological diseases</topic><topic>Neurophysiology</topic><topic>Neuroprotection</topic><topic>Phosphorylation</topic><topic>Potassium</topic><topic>Proteins</topic><topic>Regulatory sequences</topic><topic>Repressor Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Molinaro, Pasquale</au><au>Sanguigno, Luca</au><au>Casamassa, Antonella</au><au>Valsecchi, Valeria</au><au>Sirabella, Rossana</au><au>Pignataro, Giuseppe</au><au>Annunziato, Lucio</au><au>Formisano, Luigi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Emerging Role of DREAM in Healthy Brain and Neurological Diseases</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2023-05-24</date><risdate>2023</risdate><volume>24</volume><issue>11</issue><spage>9177</spage><pages>9177-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>The downstream regulatory element antagonist modulator (DREAM) is a multifunctional Ca
-sensitive protein exerting a dual mechanism of action to regulate several Ca
-dependent processes. Upon sumoylation, DREAM enters in nucleus where it downregulates the expression of several genes provided with a consensus sequence named dream regulatory element (DRE). On the other hand, DREAM could also directly modulate the activity or the localization of several cytosolic and plasma membrane proteins. In this review, we summarize recent advances in the knowledge of DREAM dysregulation and DREAM-dependent epigenetic remodeling as a central mechanism in the progression of several diseases affecting central nervous system, including stroke, Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and neuropathic pain. Interestingly, DREAM seems to exert a common detrimental role in these diseases by inhibiting the transcription of several neuroprotective genes, including the sodium/calcium exchanger isoform 3 (NCX3), brain-derived neurotrophic factor (BDNF), pro-dynorphin, and c-fos. These findings lead to the concept that DREAM might represent a pharmacological target to ameliorate symptoms and reduce neurodegenerative processes in several pathological conditions affecting central nervous system.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37298129</pmid><doi>10.3390/ijms24119177</doi><orcidid>https://orcid.org/0000-0002-1375-6304</orcidid><orcidid>https://orcid.org/0000-0002-7290-4397</orcidid><orcidid>https://orcid.org/0000-0003-2770-2267</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Amyotrophic lateral sclerosis Brain Brain - metabolism Brain-derived neurotrophic factor c-Fos protein Calcium Calcium ions Cell Nucleus - metabolism Central nervous system Conserved sequence Development and progression Dynorphin Dynorphins - metabolism Enzymes Epigenetic inheritance Epigenetics Gene expression Genes Genetic transcription Homeostasis Kinases Kv Channel-Interacting Proteins - metabolism Ligands Localization Membrane proteins Na+/Ca2+ exchanger Nervous system diseases Neurological diseases Neurophysiology Neuroprotection Phosphorylation Potassium Proteins Regulatory sequences Repressor Proteins - genetics Review Signs and symptoms SUMO protein Transcription factors |
| title | Emerging Role of DREAM in Healthy Brain and Neurological Diseases |
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