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RAGE and Parkinson's disease (PD) are closely associated, but it remains unclear whether the HMGB1\/RAGE\/NF\u2010\u03baB signaling pathway contributes to the pathophysiology of PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PD was induced by administration of 6\u2010hydroxydopamine (6\u2010OHDA), while RAGE was inhibited using an inhibitor, FPS\u2010ZM1. The grip strength test\u00a0and Morris water maze\u00a0were used to evaluate sensorimotor and memory skills. Then detect the expression levels of RAGE, HMGB1, and NF\u2010\u03baB in the striatal sample using immunohistochemistry, western blotting, and RT\u2010qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      (1) In PD rats, treatment with FPS\u2010ZM1 improved learning and memory ability and alleviated sensorimotor deficits. (2) The striatum of PD rats exhibited a significant increase in the number of HMGB1\u2010, RAGE\u2010, and NF\u2010\u03baB\u2010positive cells, which could be reduced through the administration of FPS\u2010ZM1. Immunofluorescence double\u2010labeling results indicated that NeuN\u2010positive neurons were the primary sites of HMGB1\u2010, RAGE\u2010, and NF\u2010\u03baB\u2010positive responses. Furthermore, these double\u2010labeled neurons demonstrated a significant increase following 6\u2010OHDA\u2010induced depletion of striatal dopamine (DA). However, the FPS\u2010ZM1 administration considerably attenuated these changes. (3) The treatment of FPS\u2010ZM1 significantly reduced the increase in protein expression of HMGB1, RAGE, and NF\u2010\u03baB that followed striatal DA depletion. Similarly,\n                      <jats:italic>NF\u2010\u03baB<\/jats:italic>\n                      and\n                      <jats:italic>RAGE<\/jats:italic>\n                      mRNA expression were increased by striatal DA deprivation; however, injection of FPS\u2010ZM1 significantly reduced these changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The HMGB1\/RAGE\/NF\u2010\u03baB signaling pathway plays a critical role in the pathogenesis of striatal neuronal damage in PD, highlighting its potential as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71133","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T07:34:56Z","timestamp":1769758496000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["High\u2010mobility Group Protein 1\/ Receptor for Advanced Glycation End Products\/ Nuclear Factor\u2010\u03baB Signalling Pathway Contributes to the Pathogenic Process of Striatal Neuron Impairment in the Rat Model of Parkinson's Disease"],"prefix":"10.1002","volume":"16","author":[{"given":"Yaofeng","family":"Zhu","sequence":"first","affiliation":[{"name":"Institute of Medicine, College of Medicine Jishou University  Jishou Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zean","family":"Du","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory for Cognitive and Developmental Disorders, Department of Anatomy School of Medicine, Jinan University Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linju","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory for Cognitive and Developmental Disorders, Department of Anatomy School of Medicine, Jinan University Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanlong","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"2024. \u201cEPO\u2010Dependent Activation of PI3K\/Akt\/FoxO3a Signalling Mediates Neuroprotection in In Vitro and In Vivo Models of Parkinson's Disease.\u201d |Journal of Molecular NeuroscienceAccessed June 2.https:\/\/link.springer.com\/article\/10.1007\/s12031\u2010013\u20100208\u20100."},{"key":"e_1_2_12_3_1","unstructured":"2025.JCI\u2014A Multimodal RAGE\u2010specific Inhibitor Reduces amyloid \u03b2\u2013mediated Brain Disorder in a Mouse Model of Alzheimer Disease. 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