IgGs from patients with amyotrophic lateral sclerosis and diabetes target Ca-v alpha(2)delta 1 subunits impairing islet cell function and survival
DC Field | Value | Language |
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dc.contributor.author | Shi, Yue | - |
dc.contributor.author | Park, Kyoung Sun | - |
dc.contributor.author | Kim, Seung Hyun | - |
dc.contributor.author | Yu, Jia | - |
dc.contributor.author | Zhao, Kaixuan | - |
dc.contributor.author | Yu, Lina | - |
dc.contributor.author | Oh, Ki Wook | - |
dc.contributor.author | Lee, Kayoung | - |
dc.contributor.author | Kim, Jaeyoon | - |
dc.contributor.author | Chaggar, Kanchan | - |
dc.contributor.author | Li, Yuxin | - |
dc.contributor.author | Dolphin, Annette C. | - |
dc.contributor.author | Catterall, William A. | - |
dc.contributor.author | Ryu, Sung Ho | - |
dc.contributor.author | Yang, Shao-Nian | - |
dc.contributor.author | Berggren, Per-Olof | - |
dc.date.accessioned | 2022-07-08T23:42:48Z | - |
dc.date.available | 2022-07-08T23:42:48Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2019-12 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/146711 | - |
dc.description.abstract | Patients with amyotrophic lateral sclerosis (ALS) often show hallmarks of type 2 diabetes mellitus (T2DM). However, the causal link between ALS and T2DM has remained a mystery. We now demonstrate that 60% of ALS patients with T2DM (ALS-T2DM) have sera that exaggerated K+-induced increases in cytosolic free Ca2+ concentration ([Ca2+],) in mouse islet cells. The effect was attributed to the presence of pathogenic immunoglobulin Gs (IgGs) in ALS-T2DM sera. The pathogenic IgGs immunocaptured the voltage-dependent Ca2+ (Ca-v) channel subunit Ca-v alpha(2)delta 1 in the plasma membrane enhancing Ca(v)1 channel-mediated Ca2+ influx and [Ca2+](i), resulting in impaired mitochondria! function. Consequently, impairments in [Ca2+](i) dynamics, insulin secretion, and cell viability occurred. These data reveal that patients with ALS-T2DM carry cytotoxic ALS-T2DM-IgG autoantibodies that serve as a causal link between ALS and T2DM by immunoattacking Ca-v alpha(2)delta 1 subunits. Our findings may lay the foundation for a pharmacological treatment strategy for patients suffering from a combination of these diseases. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.title | IgGs from patients with amyotrophic lateral sclerosis and diabetes target Ca-v alpha(2)delta 1 subunits impairing islet cell function and survival | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Seung Hyun | - |
dc.contributor.affiliatedAuthor | Oh, Ki Wook | - |
dc.identifier.doi | 10.1073/pnas.1911956116 | - |
dc.identifier.scopusid | 2-s2.0-85077246092 | - |
dc.identifier.wosid | 000504656900091 | - |
dc.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.116, no.52, pp.26816 - 26822 | - |
dc.relation.isPartOf | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.citation.title | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.citation.volume | 116 | - |
dc.citation.number | 52 | - |
dc.citation.startPage | 26816 | - |
dc.citation.endPage | 26822 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | PANCREATIC BETA-CELL | - |
dc.subject.keywordPlus | GATED CALCIUM-CHANNELS | - |
dc.subject.keywordPlus | GLUCOSE-TOLERANCE | - |
dc.subject.keywordPlus | IMMUNOGLOBULINS | - |
dc.subject.keywordPlus | MITOCHONDRIA | - |
dc.subject.keywordPlus | ANTIBODIES | - |
dc.subject.keywordPlus | PHYSIOLOGY | - |
dc.subject.keywordPlus | INCREASES | - |
dc.subject.keywordPlus | DEATH | - |
dc.subject.keywordPlus | SERUM | - |
dc.subject.keywordAuthor | amyotrophic lateral sclerosis | - |
dc.subject.keywordAuthor | calcium channel | - |
dc.subject.keywordAuthor | cytosolic free Ca2+ concentration | - |
dc.subject.keywordAuthor | diabetes | - |
dc.subject.keywordAuthor | immunoglobulin | - |
dc.identifier.url | https://www.pnas.org/content/116/52/26816 | - |
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