Microglia Mediated Neuroinflammation: Focus on PI3K Modulation
Identifieur interne : 000101 ( Pmc/Checkpoint ); précédent : 000100; suivant : 000102Microglia 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 when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000877</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000877</idno><idno type="wicri:Area/Pmc/Curation">000877</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000877</idno><idno type="wicri:Area/Pmc/Checkpoint">000101</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000101</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">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></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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<front><journal-meta><journal-id journal-id-type="nlm-ta">Biomolecules</journal-id><journal-id journal-id-type="iso-abbrev">Biomolecules</journal-id><journal-id journal-id-type="publisher-id">biomolecules</journal-id><journal-title-group><journal-title>Biomolecules</journal-title></journal-title-group><issn pub-type="epub">2218-273X</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31947676</article-id><article-id pub-id-type="pmc">7022557</article-id><article-id pub-id-type="doi">10.3390/biom10010137</article-id><article-id pub-id-type="publisher-id">biomolecules-10-00137</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Microglia Mediated Neuroinflammation: Focus on PI3K Modulation</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Cianciulli</surname><given-names>Antonia</given-names></name><xref ref-type="aff" rid="af1-biomolecules-10-00137">1</xref><xref ref-type="author-notes" rid="fn1-biomolecules-10-00137">†</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-7526-6968</contrib-id><name><surname>Porro</surname><given-names>Chiara</given-names></name><xref ref-type="aff" rid="af2-biomolecules-10-00137">2</xref><xref ref-type="author-notes" rid="fn1-biomolecules-10-00137">†</xref></contrib><contrib contrib-type="author"><name><surname>Calvello</surname><given-names>Rosa</given-names></name><xref ref-type="aff" rid="af1-biomolecules-10-00137">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-5693-6172</contrib-id><name><surname>Trotta</surname><given-names>Teresa</given-names></name><xref ref-type="aff" rid="af2-biomolecules-10-00137">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-0106-3615</contrib-id><name><surname>Lofrumento</surname><given-names>Dario Domenico</given-names></name><xref ref-type="aff" rid="af3-biomolecules-10-00137">3</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-5457-1069</contrib-id><name><surname>Panaro</surname><given-names>Maria Antonietta</given-names></name><xref ref-type="aff" rid="af1-biomolecules-10-00137">1</xref><xref rid="c1-biomolecules-10-00137" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-biomolecules-10-00137"><label>1</label>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.)</aff><aff id="af2-biomolecules-10-00137"><label>2</label>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.)</aff><aff id="af3-biomolecules-10-00137"><label>3</label>Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, 73100 Lecce, Italy;<email>dario.lofrumento@unisalento.it</email></aff><author-notes><corresp id="c1-biomolecules-10-00137"><label>*</label>Correspondence: <email>mariaantonietta.panaro@uniba.it</email></corresp><fn id="fn1-biomolecules-10-00137"><label>†</label><p>Both authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="epub"><day>14</day><month>1</month><year>2020</year></pub-date><pub-date pub-type="collection"><month>1</month><year>2020</year></pub-date><volume>10</volume><issue>1</issue><elocation-id>137</elocation-id><history><date date-type="received"><day>02</day><month>12</month><year>2019</year></date><date date-type="accepted"><day>10</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 by the authors.</copyright-statement><copyright-year>2020</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><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. Finally, we discuss the modulation of PI3K as a potential therapeutic approach helpful for developing innovative therapeutic strategies in neurodegenerative diseases.</p></abstract><kwd-group><kwd>neurodegeneration</kwd><kwd>inflammation</kwd><kwd>PI3K</kwd><kwd>microglia</kwd><kwd>signaling pathway</kwd></kwd-group></article-meta></front><floats-group><fig id="biomolecules-10-00137-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>The PI3K-Akt signaling pathway. The PI3K-Akt pathway is involved in some crucial cellular processes including protein synthesis and cell proliferation and survival. The PI3K/Akt pathway is activated by factors that initiate the PI3K signaling pathway via intermediate molecules (IRS), playing an important regulatory role in many cellular survival pathways. The pathway can be activated by a variety of signals, including growth factors (GF), LPS, and insulin (INS), targeting several downstream molecules. This activation is able to modulate cell activities, including cell proliferation, glucose metabolism, cell survival, cell cycle, protein synthesis, and neuronal morphology and plasticity.</p></caption><graphic xlink:href="biomolecules-10-00137-g001"></graphic></fig><fig id="biomolecules-10-00137-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>M1/M2 microglia balance depending on PI3K inhibition/activation. Pro-inflammatory microglia (M1) release pro-inflammatory cytokines, which promote neuroinflammation, depending on damage severity and duration. Microglia are able to switch to the anti-inflammatory (M2) phenotype, leading to neuroprotection. The switch and balancing between the M1/M2 phenotype can be regulated by modulating PI3K inhibition/activation.</p></caption><graphic xlink:href="biomolecules-10-00137-g002"></graphic></fig><table-wrap id="biomolecules-10-00137-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">biomolecules-10-00137-t001_Table 1</object-id><label>Table 1</label><caption><p>Tissue distribution of PI3K isoforms.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">PI3k</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Expression</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Ref</th></tr></thead><tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p110 α</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ubiquitous</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B14-biomolecules-10-00137" ref-type="bibr">14</xref>,<xref rid="B23-biomolecules-10-00137" ref-type="bibr">23</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p110 β</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ubiquitous</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B14-biomolecules-10-00137" ref-type="bibr">14</xref>,<xref rid="B23-biomolecules-10-00137" ref-type="bibr">23</xref>,<xref rid="B24-biomolecules-10-00137" ref-type="bibr">24</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p110 δ</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Immune cells, Neurons and Microglia, Spleen, Platelets, Endothelial Cells</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B25-biomolecules-10-00137" ref-type="bibr">25</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p85 α</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ubiquitous</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B24-biomolecules-10-00137" ref-type="bibr">24</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p55 α</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Brain, Muscle</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B26-biomolecules-10-00137" ref-type="bibr">26</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p50 α</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Liver, Kidney, Brain, T Cells</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B25-biomolecules-10-00137" ref-type="bibr">25</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p85 β</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ubiquitous</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B24-biomolecules-10-00137" ref-type="bibr">24</xref>,<xref rid="B26-biomolecules-10-00137" ref-type="bibr">26</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p55 γ</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Brain, Testis, Liver, Muscle, Fat, Spleen</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B24-biomolecules-10-00137" ref-type="bibr">24</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p110 γ</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Immune Cells, Heart, Pancreas, Liver, Skeletal Muscle</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B25-biomolecules-10-00137" ref-type="bibr">25</xref>,<xref rid="B27-biomolecules-10-00137" ref-type="bibr">27</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p101</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Immune Cells, Mast Cells</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B26-biomolecules-10-00137" ref-type="bibr">26</xref>,<xref rid="B28-biomolecules-10-00137" ref-type="bibr">28</xref>,<xref rid="B29-biomolecules-10-00137" ref-type="bibr">29</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>p84/p87</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Immune cells, Mast Cell, Heart</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B26-biomolecules-10-00137" ref-type="bibr">26</xref>,<xref rid="B28-biomolecules-10-00137" ref-type="bibr">28</xref>,<xref rid="B29-biomolecules-10-00137" ref-type="bibr">29</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>pI3k-C2</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ubiquitous</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B30-biomolecules-10-00137" ref-type="bibr">30</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>pI3k-C2β</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ubiquitous</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B30-biomolecules-10-00137" ref-type="bibr">30</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>pI3k-C2 γ</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Liver, Prostate, Breast, Salivary Gland</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B31-biomolecules-10-00137" ref-type="bibr">31</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Vps34</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ubiquitous</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B32-biomolecules-10-00137" ref-type="bibr">32</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Vps15</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ubiquitous</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B26-biomolecules-10-00137" ref-type="bibr">26</xref>]</td></tr></tbody></table></table-wrap><table-wrap id="biomolecules-10-00137-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">biomolecules-10-00137-t002_Table 2</object-id><label>Table 2</label><caption><p>Compounds involved in the activation/inhibition of the PI3K pathway.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Compounds</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Nature</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Function</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Ref.</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Myricetin</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Flavonoid</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B106-biomolecules-10-00137" ref-type="bibr">106</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Baicalein</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Flavonoid</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B126-biomolecules-10-00137" ref-type="bibr">126</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Apigenin</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Flavonoid</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B27-biomolecules-10-00137" ref-type="bibr">27</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Morin</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Flavonoid</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B74-biomolecules-10-00137" ref-type="bibr">74</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Quercetin</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Flavonoid</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B127-biomolecules-10-00137" ref-type="bibr">127</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Puerarin</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Flavonoid</td><td align="center" valign="middle" rowspan="1" colspan="1">Activation</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B128-biomolecules-10-00137" ref-type="bibr">128</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Hesperidin</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Flavonoid</td><td align="center" valign="middle" rowspan="1" colspan="1">Activation</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B129-biomolecules-10-00137" ref-type="bibr">129</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>EGCG</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Polyphenol</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B130-biomolecules-10-00137" ref-type="bibr">130</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Curcumin</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Polyphenol</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B57-biomolecules-10-00137" ref-type="bibr">57</xref>,<xref rid="B88-biomolecules-10-00137" ref-type="bibr">88</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Wortmannin</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">A fungal metabolite</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B131-biomolecules-10-00137" ref-type="bibr">131</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Irisin</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Hormone</td><td align="center" valign="middle" rowspan="1" colspan="1">Activation</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B132-biomolecules-10-00137" ref-type="bibr">132</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Insulin</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Hormone</td><td align="center" valign="middle" rowspan="1" colspan="1">Activation</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B133-biomolecules-10-00137" ref-type="bibr">133</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>BDNF</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Brain-derived neurotrophic factor</td><td align="center" valign="middle" rowspan="1" colspan="1">Activation</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B131-biomolecules-10-00137" ref-type="bibr">131</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>PDGF</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Platelet-derived growth factor</td><td align="center" valign="middle" rowspan="1" colspan="1">Activation</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B43-biomolecules-10-00137" ref-type="bibr">43</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>EGF</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Epidermal growth factor</td><td align="center" valign="middle" rowspan="1" colspan="1">Activation</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B43-biomolecules-10-00137" ref-type="bibr">43</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>TNFR2</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">75-kDa TNF receptor type II</td><td align="center" valign="middle" rowspan="1" colspan="1">Activation</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B134-biomolecules-10-00137" ref-type="bibr">134</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>TGF-1α</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Pleiotropic cytokine</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B135-biomolecules-10-00137" ref-type="bibr">135</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>FAM3A</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Cytokine-like gene family</td><td align="center" valign="middle" rowspan="1" colspan="1">Activation</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B136-biomolecules-10-00137" ref-type="bibr">136</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>NSE</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Neuron specific enolase</td><td align="center" valign="middle" rowspan="1" colspan="1">Activation</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B137-biomolecules-10-00137" ref-type="bibr">137</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>6-MP</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Thiopurine</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B137-biomolecules-10-00137" ref-type="bibr">137</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>LY294002</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibitor</td><td align="center" valign="middle" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B138-biomolecules-10-00137" ref-type="bibr">138</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>ZSTK474</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Class I PI3K inhibitor</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Inhibition</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B132-biomolecules-10-00137" ref-type="bibr">132</xref>]</td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list></list><tree><noCountry><name sortKey="Calvello, Rosa" sort="Calvello, Rosa" uniqKey="Calvello R" first="Rosa" last="Calvello">Rosa Calvello</name><name sortKey="Cianciulli, Antonia" sort="Cianciulli, Antonia" uniqKey="Cianciulli A" first="Antonia" last="Cianciulli">Antonia Cianciulli</name><name sortKey="Lofrumento, Dario Domenico" sort="Lofrumento, Dario Domenico" uniqKey="Lofrumento D" first="Dario Domenico" last="Lofrumento">Dario Domenico Lofrumento</name><name sortKey="Panaro, Maria Antonietta" sort="Panaro, Maria Antonietta" uniqKey="Panaro M" first="Maria Antonietta" last="Panaro">Maria Antonietta Panaro</name><name sortKey="Porro, Chiara" sort="Porro, Chiara" uniqKey="Porro C" first="Chiara" last="Porro">Chiara Porro</name><name sortKey="Trotta, Teresa" sort="Trotta, Teresa" uniqKey="Trotta T" first="Teresa" last="Trotta">Teresa Trotta</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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