Insulin-Like Growth Factor Signaling in Alzheimer’s Disease: Pathophysiology and Therapeutic Strategies
Alzheimer’s disease (AD) is the leading cause of dementia among the elderly population, posing a significant public health challenge due to limited therapeutic options that merely delay cognitive decline. AD is associated with impaired energy metabolism and reduced neurotrophic signaling. The insuli...
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| Veröffentlicht in: | Molecular neurobiology 2025-03, Vol.62 (3), p.3195-3225 |
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| creator | Miao, Jie Zhang, Yanli Su, Chen Zheng, Qiandan Guo, Junhong |
| description | Alzheimer’s disease (AD) is the leading cause of dementia among the elderly population, posing a significant public health challenge due to limited therapeutic options that merely delay cognitive decline. AD is associated with impaired energy metabolism and reduced neurotrophic signaling. The insulin-like growth factor (IGF) signaling pathway, crucial for central nervous system (CNS) development, metabolism, repair, cognition, and emotion regulation, includes IGF-1, IGF-2, IGF-1R, IGF-2R, insulin receptor (IR), and six insulin-like growth factor binding proteins (IGFBPs). Research has identified abnormalities in IGF signaling in individuals with AD and AD models. Dysregulated expression of IGFs, receptors, IGFBPs, and disruptions in downstream phosphoinositide 3-kinase-protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) pathways collectively increase AD susceptibility. Studies suggest modulating the IGF pathway may ameliorate AD pathology and cognitive decline. This review explores the CNS pathophysiology of IGF signaling in AD progression and assesses the potential of targeting the IGF system as a novel therapeutic strategy. Further research is essential to elucidate how aberrant IGF signaling contributes to AD development, understand underlying molecular mechanisms, and evaluate the safety and efficacy of IGF-based treatments. |
| doi_str_mv | 10.1007/s12035-024-04457-1 |
| format | Article |
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AD is associated with impaired energy metabolism and reduced neurotrophic signaling. The insulin-like growth factor (IGF) signaling pathway, crucial for central nervous system (CNS) development, metabolism, repair, cognition, and emotion regulation, includes IGF-1, IGF-2, IGF-1R, IGF-2R, insulin receptor (IR), and six insulin-like growth factor binding proteins (IGFBPs). Research has identified abnormalities in IGF signaling in individuals with AD and AD models. Dysregulated expression of IGFs, receptors, IGFBPs, and disruptions in downstream phosphoinositide 3-kinase-protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) pathways collectively increase AD susceptibility. Studies suggest modulating the IGF pathway may ameliorate AD pathology and cognitive decline. This review explores the CNS pathophysiology of IGF signaling in AD progression and assesses the potential of targeting the IGF system as a novel therapeutic strategy. Further research is essential to elucidate how aberrant IGF signaling contributes to AD development, understand underlying molecular mechanisms, and evaluate the safety and efficacy of IGF-based treatments.</description><identifier>ISSN: 0893-7648</identifier><identifier>ISSN: 1559-1182</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-024-04457-1</identifier><identifier>PMID: 39240280</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Alzheimer Disease - drug therapy ; Alzheimer Disease - metabolism ; Alzheimer Disease - physiopathology ; Alzheimer's disease ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Central nervous system ; Cognitive ability ; Dementia disorders ; Energy metabolism ; Humans ; Insulin ; Insulin-like growth factor I ; Insulin-like growth factor I receptors ; Insulin-like growth factors ; Insulin-Like Peptides ; Kinases ; MAP kinase ; Metabolism ; Molecular modelling ; Neurobiology ; Neurodegenerative diseases ; Neurology ; Neurosciences ; Older people ; Pathophysiology ; Public health ; Review ; Signal Transduction ; Somatomedins - metabolism</subject><ispartof>Molecular neurobiology, 2025-03, Vol.62 (3), p.3195-3225</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>Copyright Springer Nature B.V. Mar 2025</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c356t-cc68937fa4767aa9e9722aecffdaf1027cd61227aca4f19aad2f7ec5db321d503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-024-04457-1$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-024-04457-1$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39240280$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miao, Jie</creatorcontrib><creatorcontrib>Zhang, Yanli</creatorcontrib><creatorcontrib>Su, Chen</creatorcontrib><creatorcontrib>Zheng, Qiandan</creatorcontrib><creatorcontrib>Guo, Junhong</creatorcontrib><title>Insulin-Like Growth Factor Signaling in Alzheimer’s Disease: Pathophysiology and Therapeutic Strategies</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>Alzheimer’s disease (AD) is the leading cause of dementia among the elderly population, posing a significant public health challenge due to limited therapeutic options that merely delay cognitive decline. AD is associated with impaired energy metabolism and reduced neurotrophic signaling. The insulin-like growth factor (IGF) signaling pathway, crucial for central nervous system (CNS) development, metabolism, repair, cognition, and emotion regulation, includes IGF-1, IGF-2, IGF-1R, IGF-2R, insulin receptor (IR), and six insulin-like growth factor binding proteins (IGFBPs). Research has identified abnormalities in IGF signaling in individuals with AD and AD models. Dysregulated expression of IGFs, receptors, IGFBPs, and disruptions in downstream phosphoinositide 3-kinase-protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) pathways collectively increase AD susceptibility. Studies suggest modulating the IGF pathway may ameliorate AD pathology and cognitive decline. This review explores the CNS pathophysiology of IGF signaling in AD progression and assesses the potential of targeting the IGF system as a novel therapeutic strategy. Further research is essential to elucidate how aberrant IGF signaling contributes to AD development, understand underlying molecular mechanisms, and evaluate the safety and efficacy of IGF-based treatments.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer Disease - physiopathology</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Central nervous system</subject><subject>Cognitive ability</subject><subject>Dementia disorders</subject><subject>Energy metabolism</subject><subject>Humans</subject><subject>Insulin</subject><subject>Insulin-like growth factor I</subject><subject>Insulin-like growth factor I receptors</subject><subject>Insulin-like growth factors</subject><subject>Insulin-Like Peptides</subject><subject>Kinases</subject><subject>MAP kinase</subject><subject>Metabolism</subject><subject>Molecular modelling</subject><subject>Neurobiology</subject><subject>Neurodegenerative diseases</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Older people</subject><subject>Pathophysiology</subject><subject>Public health</subject><subject>Review</subject><subject>Signal Transduction</subject><subject>Somatomedins - metabolism</subject><issn>0893-7648</issn><issn>1559-1182</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EokPhBVggS2y6MfjaSTxhg6qWlkojgdSytm6dm8QlEw92ApqueA1ejyfBZUr5WbDy4nz3-Nx7GHsK8gVIaV4mUFKXQqpCyKIojYB7bAFlWQuApbrPFnJZa2GqYrnHHqV0JaVSIM1DtqdrVUi1lAvmz8Y0D34UK_-R-GkMX6aen6CbQuTnvhsxax33Iz8crnvya4rfv35L_NgnwkSv-Huc-rDpt8mHIXRbjmPDL3qKuKF58o6fTxEn6jylx-xBi0OiJ7fvPvtw8ubi6K1YvTs9OzpcCafLahLOVTm1abEwlUGsqTZKIbm2bbAFqYxrKlDKoMOihRqxUa0hVzaXWkFTSr3PXu98N_PlmhpHY44w2E30a4xbG9Dbv5XR97YLny2AqaUxJjsc3DrE8GmmNNm1T46GAUcKc7IaJOT7QVVm9Pk_6FWYY77aDVVpWSqtVabUjnIxpBSpvUsD0t5UaXdV2lyl_VmlhTz07M897kZ-dZcBvQNSlsaO4u-__2P7A98jrPc</recordid><startdate>202503</startdate><enddate>202503</enddate><creator>Miao, Jie</creator><creator>Zhang, Yanli</creator><creator>Su, Chen</creator><creator>Zheng, Qiandan</creator><creator>Guo, Junhong</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>202503</creationdate><title>Insulin-Like Growth Factor Signaling in Alzheimer’s Disease: Pathophysiology and Therapeutic Strategies</title><author>Miao, Jie ; Zhang, Yanli ; Su, Chen ; Zheng, Qiandan ; Guo, Junhong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-cc68937fa4767aa9e9722aecffdaf1027cd61227aca4f19aad2f7ec5db321d503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer Disease - physiopathology</topic><topic>Alzheimer's disease</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Central nervous system</topic><topic>Cognitive ability</topic><topic>Dementia disorders</topic><topic>Energy metabolism</topic><topic>Humans</topic><topic>Insulin</topic><topic>Insulin-like growth factor I</topic><topic>Insulin-like growth factor I receptors</topic><topic>Insulin-like growth factors</topic><topic>Insulin-Like Peptides</topic><topic>Kinases</topic><topic>MAP kinase</topic><topic>Metabolism</topic><topic>Molecular modelling</topic><topic>Neurobiology</topic><topic>Neurodegenerative diseases</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Older people</topic><topic>Pathophysiology</topic><topic>Public health</topic><topic>Review</topic><topic>Signal Transduction</topic><topic>Somatomedins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miao, Jie</creatorcontrib><creatorcontrib>Zhang, Yanli</creatorcontrib><creatorcontrib>Su, Chen</creatorcontrib><creatorcontrib>Zheng, Qiandan</creatorcontrib><creatorcontrib>Guo, Junhong</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miao, Jie</au><au>Zhang, Yanli</au><au>Su, Chen</au><au>Zheng, Qiandan</au><au>Guo, Junhong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Insulin-Like Growth Factor Signaling in Alzheimer’s Disease: Pathophysiology and Therapeutic Strategies</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2025-03</date><risdate>2025</risdate><volume>62</volume><issue>3</issue><spage>3195</spage><epage>3225</epage><pages>3195-3225</pages><issn>0893-7648</issn><issn>1559-1182</issn><eissn>1559-1182</eissn><abstract>Alzheimer’s disease (AD) is the leading cause of dementia among the elderly population, posing a significant public health challenge due to limited therapeutic options that merely delay cognitive decline. AD is associated with impaired energy metabolism and reduced neurotrophic signaling. The insulin-like growth factor (IGF) signaling pathway, crucial for central nervous system (CNS) development, metabolism, repair, cognition, and emotion regulation, includes IGF-1, IGF-2, IGF-1R, IGF-2R, insulin receptor (IR), and six insulin-like growth factor binding proteins (IGFBPs). Research has identified abnormalities in IGF signaling in individuals with AD and AD models. Dysregulated expression of IGFs, receptors, IGFBPs, and disruptions in downstream phosphoinositide 3-kinase-protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) pathways collectively increase AD susceptibility. Studies suggest modulating the IGF pathway may ameliorate AD pathology and cognitive decline. This review explores the CNS pathophysiology of IGF signaling in AD progression and assesses the potential of targeting the IGF system as a novel therapeutic strategy. Further research is essential to elucidate how aberrant IGF signaling contributes to AD development, understand underlying molecular mechanisms, and evaluate the safety and efficacy of IGF-based treatments.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>39240280</pmid><doi>10.1007/s12035-024-04457-1</doi><tpages>31</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Alzheimer Disease - drug therapy Alzheimer Disease - metabolism Alzheimer Disease - physiopathology Alzheimer's disease Animals Biomedical and Life Sciences Biomedicine Cell Biology Central nervous system Cognitive ability Dementia disorders Energy metabolism Humans Insulin Insulin-like growth factor I Insulin-like growth factor I receptors Insulin-like growth factors Insulin-Like Peptides Kinases MAP kinase Metabolism Molecular modelling Neurobiology Neurodegenerative diseases Neurology Neurosciences Older people Pathophysiology Public health Review Signal Transduction Somatomedins - metabolism |
| title | Insulin-Like Growth Factor Signaling in Alzheimer’s Disease: Pathophysiology and Therapeutic Strategies |
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