The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke
Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is criti...
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| Veröffentlicht in: | Cellular and molecular neurobiology 2023-10, Vol.43 (7), p.3435-3447 |
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| creator | Purrahman, Daryush Shojaeian, Ali Poniatowski, Łukasz A. Piechowski-Jóźwiak, Bartłomiej Mahmoudian-Sani, Mohammad-Reza |
| description | Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines.
Graphical Abstract
Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke. |
| doi_str_mv | 10.1007/s10571-023-01396-8 |
| format | Article |
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Graphical Abstract
Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke.</description><identifier>ISSN: 0272-4340</identifier><identifier>EISSN: 1573-6830</identifier><identifier>DOI: 10.1007/s10571-023-01396-8</identifier><identifier>PMID: 37561339</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; Brain injury ; Cell Biology ; Cell proliferation ; Central nervous system ; Cognitive ability ; Cytokines ; Endoplasmic reticulum ; Granulin ; Hippocampus ; Inflammation ; Ischemia ; MAP kinase ; Microglia ; Nervous system ; Neural stem cells ; Neurobiology ; Neurogenesis ; Neuroprotection ; Neurosciences ; Neurotrophic factors ; NF-κB protein ; Pathogenesis ; Reperfusion ; Review Paper ; Signal transduction ; Stroke ; Wound healing</subject><ispartof>Cellular and molecular neurobiology, 2023-10, Vol.43 (7), p.3435-3447</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-7f3b8d12dd583ccb75caee303be55a792ea80e9ec15b00482598ff172af648a33</citedby><cites>FETCH-LOGICAL-c375t-7f3b8d12dd583ccb75caee303be55a792ea80e9ec15b00482598ff172af648a33</cites><orcidid>0000-0002-1096-5661 ; 0000-0002-1166-385X ; 0000-0002-1886-9949 ; 0000-0003-4202-7984 ; 0000-0002-8215-2686</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10571-023-01396-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10571-023-01396-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37561339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Purrahman, Daryush</creatorcontrib><creatorcontrib>Shojaeian, Ali</creatorcontrib><creatorcontrib>Poniatowski, Łukasz A.</creatorcontrib><creatorcontrib>Piechowski-Jóźwiak, Bartłomiej</creatorcontrib><creatorcontrib>Mahmoudian-Sani, Mohammad-Reza</creatorcontrib><title>The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke</title><title>Cellular and molecular neurobiology</title><addtitle>Cell Mol Neurobiol</addtitle><addtitle>Cell Mol Neurobiol</addtitle><description>Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines.
Graphical Abstract
Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain injury</subject><subject>Cell Biology</subject><subject>Cell proliferation</subject><subject>Central nervous system</subject><subject>Cognitive ability</subject><subject>Cytokines</subject><subject>Endoplasmic reticulum</subject><subject>Granulin</subject><subject>Hippocampus</subject><subject>Inflammation</subject><subject>Ischemia</subject><subject>MAP kinase</subject><subject>Microglia</subject><subject>Nervous system</subject><subject>Neural stem cells</subject><subject>Neurobiology</subject><subject>Neurogenesis</subject><subject>Neuroprotection</subject><subject>Neurosciences</subject><subject>Neurotrophic factors</subject><subject>NF-κB protein</subject><subject>Pathogenesis</subject><subject>Reperfusion</subject><subject>Review Paper</subject><subject>Signal transduction</subject><subject>Stroke</subject><subject>Wound healing</subject><issn>0272-4340</issn><issn>1573-6830</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kE1PwzAMhiMEgjH4AxxQJS5wKDhJ06RHhPiSJpjGOEdp5m6FrhlJe-DfE9gAiQMnW_Lj19ZDyBGFcwogLwIFIWkKjKdAeZGnaosMqJA8zRWHbTIAJlma8Qz2yH4ILwBQAIhdsselyCnnxYBcTxeYTFyDiauSsXdzb9q-qdvkdHw7eThLYtdFYmy6hZtji6EOn-R9sAtc1jZ56rx7xQOyU5km4OGmDsnzzfX06i4dPd7eX12OUhsvdqmseKlmlM1mQnFrSymsQeTASxTCyIKhUYAFWipKgEwxUaiqopKZKs-U4XxITte5K-_eegydXtbBYtOYFl0fNFOZUhnNchHRkz_oi-t9G7-LVA4yKyhjkWJrynoXgsdKr3y9NP5dU9CfkvVaso6S9ZdkreLS8Sa6L5c4-1n5thoBvgZCHLVz9L-3_4n9ABtwhOI</recordid><startdate>20231001</startdate><enddate>20231001</enddate><creator>Purrahman, Daryush</creator><creator>Shojaeian, Ali</creator><creator>Poniatowski, Łukasz A.</creator><creator>Piechowski-Jóźwiak, Bartłomiej</creator><creator>Mahmoudian-Sani, Mohammad-Reza</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1096-5661</orcidid><orcidid>https://orcid.org/0000-0002-1166-385X</orcidid><orcidid>https://orcid.org/0000-0002-1886-9949</orcidid><orcidid>https://orcid.org/0000-0003-4202-7984</orcidid><orcidid>https://orcid.org/0000-0002-8215-2686</orcidid></search><sort><creationdate>20231001</creationdate><title>The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke</title><author>Purrahman, Daryush ; Shojaeian, Ali ; Poniatowski, Łukasz A. ; Piechowski-Jóźwiak, Bartłomiej ; Mahmoudian-Sani, Mohammad-Reza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-7f3b8d12dd583ccb75caee303be55a792ea80e9ec15b00482598ff172af648a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain injury</topic><topic>Cell Biology</topic><topic>Cell proliferation</topic><topic>Central nervous system</topic><topic>Cognitive ability</topic><topic>Cytokines</topic><topic>Endoplasmic reticulum</topic><topic>Granulin</topic><topic>Hippocampus</topic><topic>Inflammation</topic><topic>Ischemia</topic><topic>MAP kinase</topic><topic>Microglia</topic><topic>Nervous system</topic><topic>Neural stem cells</topic><topic>Neurobiology</topic><topic>Neurogenesis</topic><topic>Neuroprotection</topic><topic>Neurosciences</topic><topic>Neurotrophic factors</topic><topic>NF-κB protein</topic><topic>Pathogenesis</topic><topic>Reperfusion</topic><topic>Review Paper</topic><topic>Signal transduction</topic><topic>Stroke</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Purrahman, Daryush</creatorcontrib><creatorcontrib>Shojaeian, Ali</creatorcontrib><creatorcontrib>Poniatowski, Łukasz A.</creatorcontrib><creatorcontrib>Piechowski-Jóźwiak, Bartłomiej</creatorcontrib><creatorcontrib>Mahmoudian-Sani, Mohammad-Reza</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cellular and molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Purrahman, Daryush</au><au>Shojaeian, Ali</au><au>Poniatowski, Łukasz A.</au><au>Piechowski-Jóźwiak, Bartłomiej</au><au>Mahmoudian-Sani, Mohammad-Reza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke</atitle><jtitle>Cellular and molecular neurobiology</jtitle><stitle>Cell Mol Neurobiol</stitle><addtitle>Cell Mol Neurobiol</addtitle><date>2023-10-01</date><risdate>2023</risdate><volume>43</volume><issue>7</issue><spage>3435</spage><epage>3447</epage><pages>3435-3447</pages><issn>0272-4340</issn><eissn>1573-6830</eissn><abstract>Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines.
Graphical Abstract
Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>37561339</pmid><doi>10.1007/s10571-023-01396-8</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-1096-5661</orcidid><orcidid>https://orcid.org/0000-0002-1166-385X</orcidid><orcidid>https://orcid.org/0000-0002-1886-9949</orcidid><orcidid>https://orcid.org/0000-0003-4202-7984</orcidid><orcidid>https://orcid.org/0000-0002-8215-2686</orcidid></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Apoptosis Biomedical and Life Sciences Biomedicine Brain injury Cell Biology Cell proliferation Central nervous system Cognitive ability Cytokines Endoplasmic reticulum Granulin Hippocampus Inflammation Ischemia MAP kinase Microglia Nervous system Neural stem cells Neurobiology Neurogenesis Neuroprotection Neurosciences Neurotrophic factors NF-κB protein Pathogenesis Reperfusion Review Paper Signal transduction Stroke Wound healing |
| title | The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke |
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