{"title":"泛素蛋白酶体系统功能障碍导致的 NDRG1 上调加重了神经退行性变。","authors":"Tomonori Hoshino, Atsushi Mukai, Hirofumi Yamashita, Hidemi Misawa, Makoto Urushitani, Yoshitaka Tashiro, Shu-Ichi Matsuzawa, Ryosuke Takahashi","doi":"10.1186/s13041-024-01150-1","DOIUrl":null,"url":null,"abstract":"<p><p>Protein turnover is crucial for cell survival, and the impairment of proteostasis leads to cell death. Aging is associated with a decline in proteostasis, as the progressive accumulation of damaged proteins is a hallmark of age-related disorders such as neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We previously discovered that the declining function of the ubiquitin-proteasome system (UPS) in motor neurons contributes to sporadic ALS pathologies, such as progressive motor neuron loss, protein accumulation, and glial activation. However, the mechanisms of UPS dysfunction-induced cell damage, such as cell death and aggregation, are not fully understood. This study used transcriptome analysis of motor neurons with UPS dysfunction and found that the expression of N-myc downstream regulated 1 (NDRG1) gets upregulated by UPS dysfunction. Additionally, the upregulation of NDRG1 induces cell death in the Neuro2a mouse neuroblastoma cell line. These results suggest that NDRG1 is a potential marker for UPS dysfunction and may play a role in neurodegeneration, such as that seen in ALS.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"77"},"PeriodicalIF":3.3000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515609/pdf/","citationCount":"0","resultStr":"{\"title\":\"NDRG1 upregulation by ubiquitin proteasome system dysfunction aggravates neurodegeneration.\",\"authors\":\"Tomonori Hoshino, Atsushi Mukai, Hirofumi Yamashita, Hidemi Misawa, Makoto Urushitani, Yoshitaka Tashiro, Shu-Ichi Matsuzawa, Ryosuke Takahashi\",\"doi\":\"10.1186/s13041-024-01150-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Protein turnover is crucial for cell survival, and the impairment of proteostasis leads to cell death. Aging is associated with a decline in proteostasis, as the progressive accumulation of damaged proteins is a hallmark of age-related disorders such as neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We previously discovered that the declining function of the ubiquitin-proteasome system (UPS) in motor neurons contributes to sporadic ALS pathologies, such as progressive motor neuron loss, protein accumulation, and glial activation. However, the mechanisms of UPS dysfunction-induced cell damage, such as cell death and aggregation, are not fully understood. This study used transcriptome analysis of motor neurons with UPS dysfunction and found that the expression of N-myc downstream regulated 1 (NDRG1) gets upregulated by UPS dysfunction. Additionally, the upregulation of NDRG1 induces cell death in the Neuro2a mouse neuroblastoma cell line. These results suggest that NDRG1 is a potential marker for UPS dysfunction and may play a role in neurodegeneration, such as that seen in ALS.</p>\",\"PeriodicalId\":18851,\"journal\":{\"name\":\"Molecular Brain\",\"volume\":\"17 1\",\"pages\":\"77\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515609/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Brain\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13041-024-01150-1\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Brain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13041-024-01150-1","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
NDRG1 upregulation by ubiquitin proteasome system dysfunction aggravates neurodegeneration.
Protein turnover is crucial for cell survival, and the impairment of proteostasis leads to cell death. Aging is associated with a decline in proteostasis, as the progressive accumulation of damaged proteins is a hallmark of age-related disorders such as neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We previously discovered that the declining function of the ubiquitin-proteasome system (UPS) in motor neurons contributes to sporadic ALS pathologies, such as progressive motor neuron loss, protein accumulation, and glial activation. However, the mechanisms of UPS dysfunction-induced cell damage, such as cell death and aggregation, are not fully understood. This study used transcriptome analysis of motor neurons with UPS dysfunction and found that the expression of N-myc downstream regulated 1 (NDRG1) gets upregulated by UPS dysfunction. Additionally, the upregulation of NDRG1 induces cell death in the Neuro2a mouse neuroblastoma cell line. These results suggest that NDRG1 is a potential marker for UPS dysfunction and may play a role in neurodegeneration, such as that seen in ALS.
期刊介绍:
Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings.
Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.