{"title":"通过消融模型探索α-Syn的功能:生理和病理意义。","authors":"Anjali Praveen, Godfried Dougnon, Hideaki Matsui","doi":"10.1007/s10571-025-01560-2","DOIUrl":null,"url":null,"abstract":"<p><p>A significant advancement in neurodegenerative research was the discovery that α-synuclein (α-Syn/SNCA) plays a part in the pathophysiology of Parkinson's disease (PD). Decades later, the protein's significant impacts on various brain disorders are still being extensively explored. In disease conditions, α-Syn misfolds and forms abnormal aggregates that accumulate in neurons, thus triggering various organellar dysfunctions and ultimately neurodegeneration. These misfolded forms are highly heterogeneous and vary significantly among different synucleinopathies, such as PD, Multiple System Atrophy, or Dementia with Lewy bodies. Though initially believed to be exclusively localized in the brain, numerous pieces of evidence suggest that α-Syn functions transcend the central nervous system, with roles in peripheral functions, such as modulation of immune responses, hematopoiesis, and gastrointestinal regulation. Here, we aim to provide a detailed compilation of cellular functions and pathological phenotypes that are altered upon attenuation of α-Syn function in vitro and in vivo and explore the effects of SNCA gene silencing in healthy and disease states using cellular and animal models.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"44"},"PeriodicalIF":3.6000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089638/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring α-Syn's Functions Through Ablation Models: Physiological and Pathological Implications.\",\"authors\":\"Anjali Praveen, Godfried Dougnon, Hideaki Matsui\",\"doi\":\"10.1007/s10571-025-01560-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>A significant advancement in neurodegenerative research was the discovery that α-synuclein (α-Syn/SNCA) plays a part in the pathophysiology of Parkinson's disease (PD). Decades later, the protein's significant impacts on various brain disorders are still being extensively explored. In disease conditions, α-Syn misfolds and forms abnormal aggregates that accumulate in neurons, thus triggering various organellar dysfunctions and ultimately neurodegeneration. These misfolded forms are highly heterogeneous and vary significantly among different synucleinopathies, such as PD, Multiple System Atrophy, or Dementia with Lewy bodies. Though initially believed to be exclusively localized in the brain, numerous pieces of evidence suggest that α-Syn functions transcend the central nervous system, with roles in peripheral functions, such as modulation of immune responses, hematopoiesis, and gastrointestinal regulation. Here, we aim to provide a detailed compilation of cellular functions and pathological phenotypes that are altered upon attenuation of α-Syn function in vitro and in vivo and explore the effects of SNCA gene silencing in healthy and disease states using cellular and animal models.</p>\",\"PeriodicalId\":9742,\"journal\":{\"name\":\"Cellular and Molecular Neurobiology\",\"volume\":\"45 1\",\"pages\":\"44\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-05-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089638/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular and Molecular Neurobiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10571-025-01560-2\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular and Molecular Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10571-025-01560-2","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Exploring α-Syn's Functions Through Ablation Models: Physiological and Pathological Implications.
A significant advancement in neurodegenerative research was the discovery that α-synuclein (α-Syn/SNCA) plays a part in the pathophysiology of Parkinson's disease (PD). Decades later, the protein's significant impacts on various brain disorders are still being extensively explored. In disease conditions, α-Syn misfolds and forms abnormal aggregates that accumulate in neurons, thus triggering various organellar dysfunctions and ultimately neurodegeneration. These misfolded forms are highly heterogeneous and vary significantly among different synucleinopathies, such as PD, Multiple System Atrophy, or Dementia with Lewy bodies. Though initially believed to be exclusively localized in the brain, numerous pieces of evidence suggest that α-Syn functions transcend the central nervous system, with roles in peripheral functions, such as modulation of immune responses, hematopoiesis, and gastrointestinal regulation. Here, we aim to provide a detailed compilation of cellular functions and pathological phenotypes that are altered upon attenuation of α-Syn function in vitro and in vivo and explore the effects of SNCA gene silencing in healthy and disease states using cellular and animal models.
期刊介绍:
Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.