{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:13:14Z","timestamp":1791267194235,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"the Project of Hainan Association for Science and Technology of Youth Science and Talents","award":["QCXM202023"],"award-info":[{"award-number":["QCXM202023"]}]},{"name":"Hainan Provincial Natural Science Foundation of China","award":["821QN260"],"award-info":[{"award-number":["821QN260"]}]},{"name":"Provincial Natural Science Foundation of China","award":["821RC698"],"award-info":[{"award-number":["821RC698"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Parkinson 's disease (PD) is a common neurodegenerative disease. Aggregates formed by \u03b1-synuclein (\u03b1-Syn) are the main pathological changes of PD. In this study, the effects of Calcium homeostasis modulator 2 (Calhm2) on \u03b1-syn-induced neurotoxicity in PD were evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Primary neurons were treated with \u03b1-Syn PFF to mimic the PD cellular model. Genes and proteins were evaluated utilizing RT-qPCR, Western blot and immunofluorescence, respectively. Cell damage was assessed using CCK-8 and LDH assay. Cellular oxidative stress was assessed via the detection of SOD, GSH and ROS level. Mitochondrial membrane potential, ATP level, AIF nuclear translocation and intracellular Ca2+ were determined for the assessment of Parthanatos. HE and immunofluorescence of TH and NeuN was detected pathological changes in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\u03b1-Syn PFF administration greatly resulted in oxidative stress, calcium overload and PARP-1 dependent Parthanatos in primary neurons. Following \u03b1-Syn PFF administration, Calhm2 and Calhm3, key calcium homeostasis modulator (Calhm) proteins, were markedly elevated in neurons, while Calhm1 expression exhibited a little change. In addition, suppression of Calhm2 obviously mitigated \u03b1-Syn PFF-induced oxidative stress injury, calcium overload and PARP-1 dependent Parthanatos in vitro. Similarly, in vivo results demonstrated that \u03b1-Syn PFF treatment led to PARP-1-dependent Parthanatos and nerve injury, while these effects were reversed by Calhm2 knockdown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Calhm2 repression lightened \u03b1-Syn aggregation-induced neurotoxicity and PARP-1-dependent Parthanatos in PD, providing a novel therapeutic target for PD treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/hmg\/ddaf091","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T08:36:26Z","timestamp":1750062986000},"page":"1419-1431","source":"Crossref","is-referenced-by-count":4,"title":["<i>Calcium homeostasis modulator 2<\/i> aggravates <i>\u03b1-synuclein<\/i>-induced neurotoxicity in Parkinson\u2019s disease by activating <i>PARP-1<\/i> depended Parthanatos"],"prefix":"10.1093","volume":"34","author":[{"given":"Qi","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University , No. 31 Longhua Road, Longhua District, Haikou 570102 ,","place":["China"]},{"name":"Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , No. 107 Yanjiangxi Road, Yuexiu District, Guangzhou 510120 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanjun","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Science, Qiongtai Normal University , No. 8 Zhongshan Road, Qiongshan District, Haikou 571100 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyu","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Fourth Affiliated Hospital of Soochow University , No. 9 Chongwen Road, Gongyeyuan District, Suzhou 215000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University , No. 31 Longhua Road, Longhua District, Haikou 570102 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University , No. 31 Longhua Road, Longhua District, Haikou 570102 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Life Sciences, Hainan Medical University , No. 3 Xueyuan Road, Longhua District, Haikou 571199 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