Microglia Mediated Neuroinflammation: Focus on PI3K Modulation
Identifieur interne : 000108 ( an2020/Analysis ); précédent : 000107; suivant : 000109Microglia Mediated Neuroinflammation: Focus on PI3K Modulation
Auteurs : Antonia Cianciulli ; Chiara Porro ; Rosa Calvello ; Teresa Trotta ; Dario Domenico Lofrumento ; Maria Antonietta PanaroSource :
- Biomolecules [ 2218-273X ] ; 2020.
Abstract
Immune activation in the central nervous system involves mostly microglia in response to pathogen invasion or tissue damage, which react, promoting a self-limiting inflammatory response aimed to restore homeostasis. However, prolonged, uncontrolled inflammation may result in the production by microglia of neurotoxic factors that lead to the amplification of the disease state and tissue damage. In particular, specific inducers of inflammation associated with neurodegenerative diseases activate inflammatory processes that result in the production of a number of mediators and cytokines that enhance neurodegenerative processes. Phosphoinositide 3-kinases (PI3Ks) constitute a family of enzymes regulating a wide range of activity, including signal transduction. Recent studies have focused attention on the intracellular role of PI3K and its contribution to neurodegenerative processes. This review illustrates and discusses recent findings about the role of this signaling pathway in the modulation of microglia neuroinflammatory responses linked to neurodegeneration. Finally, we discuss the modulation of PI3K as a potential therapeutic approach helpful for developing innovative therapeutic strategies in neurodegenerative diseases.
Url:
DOI: 10.3390/biom10010137
PubMed: 31947676
PubMed Central: 7022557
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Microglia Mediated Neuroinflammation: Focus on PI3K Modulation</title><author><name sortKey="Cianciulli, Antonia" sort="Cianciulli, Antonia" uniqKey="Cianciulli A" first="Antonia" last="Cianciulli">Antonia Cianciulli</name><affiliation><nlm:aff id="af1-biomolecules-10-00137">Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy;<email>antonia.cianciulli@uniba.it</email> (A.C.);<email>rosa.calvello@uniba.it</email> (R.C.)</nlm:aff></affiliation></author><author><name sortKey="Porro, Chiara" sort="Porro, Chiara" uniqKey="Porro C" first="Chiara" last="Porro">Chiara Porro</name><affiliation><nlm:aff id="af2-biomolecules-10-00137">Department of Clinical and Experimental Medicine, University of Foggia, 71100 Foggia, Italy;<email>chiara.porro@unifg.it</email> (C.P.);<email>teresa.trotta@unifg.it</email> (T.T.)</nlm:aff></affiliation></author><author><name sortKey="Calvello, Rosa" sort="Calvello, Rosa" uniqKey="Calvello R" first="Rosa" last="Calvello">Rosa Calvello</name><affiliation><nlm:aff id="af1-biomolecules-10-00137">Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy;<email>antonia.cianciulli@uniba.it</email> (A.C.);<email>rosa.calvello@uniba.it</email> (R.C.)</nlm:aff></affiliation></author><author><name sortKey="Trotta, Teresa" sort="Trotta, Teresa" uniqKey="Trotta T" first="Teresa" last="Trotta">Teresa Trotta</name><affiliation><nlm:aff id="af2-biomolecules-10-00137">Department of Clinical and Experimental Medicine, University of Foggia, 71100 Foggia, Italy;<email>chiara.porro@unifg.it</email> (C.P.);<email>teresa.trotta@unifg.it</email> (T.T.)</nlm:aff></affiliation></author><author><name sortKey="Lofrumento, Dario Domenico" sort="Lofrumento, Dario Domenico" uniqKey="Lofrumento D" first="Dario Domenico" last="Lofrumento">Dario Domenico Lofrumento</name><affiliation><nlm:aff id="af3-biomolecules-10-00137">Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, 73100 Lecce, Italy;<email>dario.lofrumento@unisalento.it</email></nlm:aff></affiliation></author><author><name sortKey="Panaro, Maria Antonietta" sort="Panaro, Maria Antonietta" uniqKey="Panaro M" first="Maria Antonietta" last="Panaro">Maria Antonietta Panaro</name><affiliation><nlm:aff id="af1-biomolecules-10-00137">Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy;<email>antonia.cianciulli@uniba.it</email> (A.C.);<email>rosa.calvello@uniba.it</email> (R.C.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31947676</idno><idno type="pmc">7022557</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022557</idno><idno type="RBID">PMC:7022557</idno><idno type="doi">10.3390/biom10010137</idno><date 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Antonia" sort="Cianciulli, Antonia" uniqKey="Cianciulli A" first="Antonia" last="Cianciulli">Antonia Cianciulli</name><affiliation><nlm:aff id="af1-biomolecules-10-00137">Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy;<email>antonia.cianciulli@uniba.it</email> (A.C.);<email>rosa.calvello@uniba.it</email> (R.C.)</nlm:aff></affiliation></author><author><name sortKey="Porro, Chiara" sort="Porro, Chiara" uniqKey="Porro C" first="Chiara" last="Porro">Chiara Porro</name><affiliation><nlm:aff id="af2-biomolecules-10-00137">Department of Clinical and Experimental Medicine, University of Foggia, 71100 Foggia, Italy;<email>chiara.porro@unifg.it</email> (C.P.);<email>teresa.trotta@unifg.it</email> (T.T.)</nlm:aff></affiliation></author><author><name sortKey="Calvello, Rosa" sort="Calvello, Rosa" uniqKey="Calvello R" first="Rosa" last="Calvello">Rosa Calvello</name><affiliation><nlm:aff id="af1-biomolecules-10-00137">Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy;<email>antonia.cianciulli@uniba.it</email> (A.C.);<email>rosa.calvello@uniba.it</email> (R.C.)</nlm:aff></affiliation></author><author><name sortKey="Trotta, Teresa" sort="Trotta, Teresa" uniqKey="Trotta T" first="Teresa" last="Trotta">Teresa Trotta</name><affiliation><nlm:aff id="af2-biomolecules-10-00137">Department of Clinical and Experimental Medicine, University of Foggia, 71100 Foggia, Italy;<email>chiara.porro@unifg.it</email> (C.P.);<email>teresa.trotta@unifg.it</email> (T.T.)</nlm:aff></affiliation></author><author><name sortKey="Lofrumento, Dario Domenico" sort="Lofrumento, Dario Domenico" uniqKey="Lofrumento D" first="Dario Domenico" last="Lofrumento">Dario Domenico Lofrumento</name><affiliation><nlm:aff id="af3-biomolecules-10-00137">Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, 73100 Lecce, Italy;<email>dario.lofrumento@unisalento.it</email></nlm:aff></affiliation></author><author><name sortKey="Panaro, Maria Antonietta" sort="Panaro, Maria Antonietta" uniqKey="Panaro M" first="Maria Antonietta" last="Panaro">Maria Antonietta Panaro</name><affiliation><nlm:aff id="af1-biomolecules-10-00137">Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy;<email>antonia.cianciulli@uniba.it</email> (A.C.);<email>rosa.calvello@uniba.it</email> (R.C.)</nlm:aff></affiliation></author></analytic><series><title level="j">Biomolecules</title><idno type="eISSN">2218-273X</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Immune activation in the central nervous system involves mostly microglia in response to pathogen invasion or tissue damage, which react, promoting a self-limiting inflammatory response aimed to restore homeostasis. However, prolonged, uncontrolled inflammation may result in the production by microglia of neurotoxic factors that lead to the amplification of the disease state and tissue damage. In particular, specific inducers of inflammation associated with neurodegenerative diseases activate inflammatory processes that result in the production of a number of mediators and cytokines that enhance neurodegenerative processes. Phosphoinositide 3-kinases (PI3Ks) constitute a family of enzymes regulating a wide range of activity, including signal transduction. Recent studies have focused attention on the intracellular role of PI3K and its contribution to neurodegenerative processes. This review illustrates and discusses recent findings about the role of this signaling pathway in the modulation of microglia neuroinflammatory responses linked to neurodegeneration. 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