JSM neurosurgery and spine最新文献

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Proteinopathies and Neurotrauma: Update on Degenerative Cascades. 蛋白质病与神经创伤：退化级联的最新进展。

JSM neurosurgery and spine Pub Date : 2022-01-01 Epub Date: 2022-09-21

Stephan Quintin, Zachary A Sorrentino, Yusuf Mehkri, Sai Sriram, Sydney Weisman, Caroline Grace Davidson, Grace M Lloyd, Eric Sung, John W Figg, Brandon Lucke-Wold

{"title":"Proteinopathies and Neurotrauma: Update on Degenerative Cascades.","authors":"Stephan Quintin, Zachary A Sorrentino, Yusuf Mehkri, Sai Sriram, Sydney Weisman, Caroline Grace Davidson, Grace M Lloyd, Eric Sung, John W Figg, Brandon Lucke-Wold","doi":"","DOIUrl":"","url":null,"abstract":"Neurotrauma, especially repetitive neurotrauma, is associated with the development of progressive neurodegeneration leading to chronic traumatic encephalopathy (CTE). Exposure to neurotrauma regularly occurs during sports and military service, often not requiring medical care. However, exposure to severe and/or repeated sub-clinical neurotrauma has been shown cause physical and psychological disability, leading to reduce life expectancy. Misfolding of proteins, or proteinopathy, is a pathological hallmark of CTE, in which chronic injury leads to local and diffuse protein aggregates. These aggregates are an overlapping feature of many neurodegenerative diseases such as CTE, Alzheimer's Disease, Parkinsons disease. Neurotrauma is also a significant risk factor for the development of these diseases, however the mechanism's underlying this association are not well understood. While phosphorylated tau aggregates are the primary feature of CTE, amyloid-beta, Transactive response DNA-binding protein 43 (TDP-43), and alpha-synuclein (αSyn) are also well documented. Aberrant misfolding of these proteins has been shown to disrupt brain homeostasis leading to neurodegeneration in a disease dependent manor. In CTE, the interaction between proteinopathies and their associated neurodegeneration is a current area of study. Here we provide an update on current literature surrounding the prevalence, characteristics, and pathogenesis of proteinopathies in CTE.","PeriodicalId":92091,"journal":{"name":"JSM neurosurgery and spine","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35346375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuronal Ablation of IKK2 Decreases Lesion Size and Improves Functional Outcome after Spinal Cord Injury in Mice. 在小鼠脊髓损伤后，IKK2神经元消融可减少病变大小并改善功能预后。

JSM neurosurgery and spine Pub Date : 2017-01-01 Epub Date: 2017-08-10

Ditte Gry Ellman, Hans Gram Novrup, Louise Helskov Jørgensen, Minna Christiansen Lund, Minna Yli-Karjanmaa, Pernille Marie Madsen, Jonas Heinrich Vienhues, Safinaz Dursun, John R Bethea, Karin Lykke-Hartmann, Roberta Brambilla, Kate Lykke Lambertsen

{"title":"Neuronal Ablation of IKK2 Decreases Lesion Size and Improves Functional Outcome after Spinal Cord Injury in Mice.","authors":"Ditte Gry Ellman, Hans Gram Novrup, Louise Helskov Jørgensen, Minna Christiansen Lund, Minna Yli-Karjanmaa, Pernille Marie Madsen, Jonas Heinrich Vienhues, Safinaz Dursun, John R Bethea, Karin Lykke-Hartmann, Roberta Brambilla, Kate Lykke Lambertsen","doi":"","DOIUrl":"","url":null,"abstract":"Nuclear factor-kappa B (NF-κB) is a key modulator of inflammation and secondary injury responses in neurodegenerative disease, including spinal cord injury (SCI). Inhibition of astroglial NF-κB reduces inflammation, enhances oligodendrogenesis and improves functional recovery after SCI, however the contribution of neuronal NF-κB to secondary inflammatory responses following SCI has yet to be investigated. We demonstrate that conditional ablation of IKK2 in Synapsin 1-expressing neurons in mice (Syn1creIKK2fl/fl) reduces activation of the classical NF-κB signaling pathway, resulting in impaired motor function and altered memory retention under naïve conditions. Following induction of a moderate SCI phosphorylated NF-κB levels decreased in the spinal cord of Syn1creIKK2fl/fl mice compared to controls, resulting in improvement in functional recovery. Histologically, Syn1creIKK2fl/fl mice exhibited reduced lesion volume but comparable microglial/leukocyte responses after SCI. In parallel, interleukin (IL)-1β expression was significantly decreased within the lesioned spinal cord, whereas IL-5, IL-6, IL-10, tumor necrosis factor (TNF) and chemokine (C-X-C motif) ligand 1 were unchanged compared to control mice. We conclude that conditional ablation of IKK2 in neurons, resulting in reduced neuronal NF-B signaling, and lead to protective effects after SCI and propose the neuronal classical NF-κB pathway as a potential target for the development of new therapeutic, neuroprotective strategies for SCI.","PeriodicalId":92091,"journal":{"name":"JSM neurosurgery and spine","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051723/pdf/nihms926632.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36334959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0