Journal of Neuropathology & Experimental Neurology最新文献_第2页

The Search for a Peripheral Biopsy Indicator of &agr;-Synuclein Pathology for Parkinson Disease 寻找帕金森病&agr;-突触核蛋白病理的外周活检指标

Journal of Neuropathology & Experimental Neurology Pub Date : 2017-01-01 DOI: 10.1093/jnen/nlw103

John M. Lee, P. Derkinderen, J. Kordower, R. Freeman, D. Munoz, T. Kremer, W. Zago, S. Hutten, C. Adler, G. Serrano, T. Beach

{"title":"The Search for a Peripheral Biopsy Indicator of &agr;-Synuclein Pathology for Parkinson Disease","authors":"John M. Lee, P. Derkinderen, J. Kordower, R. Freeman, D. Munoz, T. Kremer, W. Zago, S. Hutten, C. Adler, G. Serrano, T. Beach","doi":"10.1093/jnen/nlw103","DOIUrl":"https://doi.org/10.1093/jnen/nlw103","url":null,"abstract":"The neuropathological hallmark of Parkinson disease (PD) is abnormal accumulation of &agr;-synuclein (&agr;-syn). Demonstrating pathological &agr;-syn in live patients would be useful for identifying and monitoring PD patients. To date, however, imaging and biofluid approaches have not permitted premortem assessment of pathological &agr;-syn. &agr;-syn pathology in the peripheral nervous system of patients with PD has been demonstrated in studies dating back more than 40 years. More recent work suggests that colon, submandibular gland and skin biopsies could be useful as expedient biomarkers but histological differentiation of pathological and normal peripheral &agr;-syn has been challenging and multiple research groups have reported variable results. A variety of immunohistochemical methods have been employed but almost all studies to date originated at single centers with no independent, blinded replication. To address these issues, the Michael J. Fox Foundation for Parkinson’s Research sponsored a series of meetings and investigations by several research groups with relevant experience. The major finding reported herein was that biopsies can be used to distinguish PD patients from normal subjects. However, full assessment of the clinical potential of biopsy will only be achieved through large, multicenter trials in which both the initial detection methodology and histology have been assessed by blinded panels of pathologists.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78807413","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: 66

DNA Methylation Profiles of Selected Pro-Inflammatory Cytokines in Alzheimer Disease 阿尔茨海默病中选定的促炎细胞因子的DNA甲基化谱

Journal of Neuropathology & Experimental Neurology Pub Date : 2017-01-01 DOI: 10.1093/jnen/nlw099

Vincenzina Nicolia, R. Cavallaro, Irene López‐González, M. Maccarrone, S. Scarpa, I. Ferrer, A. Fuso

{"title":"DNA Methylation Profiles of Selected Pro-Inflammatory Cytokines in Alzheimer Disease","authors":"Vincenzina Nicolia, R. Cavallaro, Irene López‐González, M. Maccarrone, S. Scarpa, I. Ferrer, A. Fuso","doi":"10.1093/jnen/nlw099","DOIUrl":"https://doi.org/10.1093/jnen/nlw099","url":null,"abstract":"By means of functional genomics analysis, we recently described the mRNA expression profiles of various genes involved in the neuroinflammatory response in the brains of subjects with late-onset Alzheimer Disease (LOAD). Some of these genes, namely interleukin (IL)-1&bgr; and IL-6, showed distinct expression profiles with peak expression during the first stages of the disease and control-like levels at later stages. IL-1&bgr; and IL-6 genes are modulated by DNA methylation in different chronic and degenerative diseases; it is also well known that LOAD may have an epigenetic basis. Indeed, we and others have previously reported gene-specific DNA methylation alterations in LOAD and in related animal models. Based on these data, we studied the DNA methylation profiles, at single cytosine resolution, of IL-1&bgr; and IL-6 5’-flanking region by bisulphite modification in the cortex of healthy controls and LOAD patients at 2 different disease stages: Braak I-II/A and Braak V-VI/C. Our analysis provides evidence that neuroinflammation in LOAD is associated with (and possibly mediated by) epigenetic modifications.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86093406","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: 58

Performance of a Condensed Protocol That Reduces Effort and Cost of NIA-AA Guidelines for Neuropathologic Assessment of Alzheimer Disease 减少NIA-AA阿尔茨海默病神经病理学评估指南的工作量和成本的精简方案的性能

Journal of Neuropathology & Experimental Neurology Pub Date : 2017-01-01 DOI: 10.1093/jnen/nlw104

Margaret E. Flanagan, Desiree A. Marshall, J. B. Shofer, K. Montine, Peter T. Nelson, T. Montine, C. D. Keene

{"title":"Performance of a Condensed Protocol That Reduces Effort and Cost of NIA-AA Guidelines for Neuropathologic Assessment of Alzheimer Disease","authors":"Margaret E. Flanagan, Desiree A. Marshall, J. B. Shofer, K. Montine, Peter T. Nelson, T. Montine, C. D. Keene","doi":"10.1093/jnen/nlw104","DOIUrl":"https://doi.org/10.1093/jnen/nlw104","url":null,"abstract":"Concerns regarding resource expenditures have been expressed about the 2012 NIA-AA Sponsored Guidelines for neuropathologic assessment of Alzheimer disease (AD) and related dementias. Here, we investigated a cost-reducing Condensed Protocol and its effectiveness in maintaining the diagnostic performance of Guidelines in assessing AD, Lewy body disease (LBD), microvascular brain injury, hippocampal sclerosis (HS), and congophilic amyloid angiopathy (CAA). The Condensed Protocol consolidates the same 20 regions into 5 tissue cassettes at ∼75% lower cost. A 28 autopsy brain–retrospective cohort was selected for varying levels of neuropathologic features in the Guidelines (Original Protocol), as well as an 18 consecutive autopsy brain prospective cohort. Three neuropathologists at 2 sites performed blinded evaluations of these cases. Lesion specificity was similar between Original and Condensed Protocols. Sensitivities for AD neuropathologic change, LBD, HS, and CAA were not substantially impacted by the Condensed Protocol, whereas sensitivity for microvascular lesions (MVLs) was decreased. Specificity for CAA was decreased using the Condensed Protocol when compared with the Original Protocol. Our results show that the Condensed Protocol is a viable alternative to the NIA-AA guidelines for AD neuropathologic change, LBD, and HS, but not MVLs or CAA, and may be a practical alternative in some practice settings.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89661321","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: 8

TERT Promoter Mutations but not the Alternative Lengthening of Telomeres Phenotype Are Present in a Subset of Ependymomas and Are Associated With Adult Onset and Progression to Ependymosarcoma TERT启动子突变而不是端粒表型的选择性延长存在于室管膜瘤的一个子集中，并且与成人室管膜肉瘤的发病和进展有关

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-12-31 DOI: 10.1093/jnen/nlw106

Fabienne Brügger, M. Dettmer, M. Neuenschwander, A. Perren, I. Marinoni, E. Hewer

{"title":"TERT Promoter Mutations but not the Alternative Lengthening of Telomeres Phenotype Are Present in a Subset of Ependymomas and Are Associated With Adult Onset and Progression to Ependymosarcoma","authors":"Fabienne Brügger, M. Dettmer, M. Neuenschwander, A. Perren, I. Marinoni, E. Hewer","doi":"10.1093/jnen/nlw106","DOIUrl":"https://doi.org/10.1093/jnen/nlw106","url":null,"abstract":"Genetic signatures related to telomere maintenance have emerged as powerful classifiers among CNS tumors. These include the alternative lengthening of telomeres (ALT) phenotype associated with mutations in the ATRX and DAXX genes and recurrent point mutations in the TERT gene promoter. We investigated a patient cohort covering the entire spectrum of childhood and adult ependymomas (n = 128), including subependymomas and myxopapillary ependymomas, for the presence of TERT promoter mutations, for loss of ATRX or DAXX expression by immunohistochemistry (as surrogates as underlying gene mutations), and for the ALT phenotype by fluorescence in situ hybridization (FISH). TERT promoter mutations were identified in 9/120 (7%) of tumors, all of which were conventional ependymomas occurring in adults. TERT promoter mutations were associated with older age and intracranial localization. Remarkably, 2 of these tumors progressed to ependymosarcoma upon recurrence. No tumors displayed an ALT phenotype by FISH or were ATRX or DAXX deficient by immunohistochemistry. In sum, TERT promoter mutations are present in a subset of mostly intracranial conventional ependymomas in adults and may be relevant for the uncommon progression to ependymosarcoma. Loss of ATRX immunoreactivity is a useful marker to rule out ependymoma in specific diagnostic settings.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91270863","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: 12

Native Oligodendrocytes in Astrocytomas Might Inhibit Tumor Proliferation by WIF1 Expression 星形细胞瘤中天然少突胶质细胞可能通过表达WIF1抑制肿瘤增殖

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-12-31 DOI: 10.1093/jnen/nlw098

M. Asslaber, S. Schauer, M. Gogg‐Kamerer, E. Bernhart, F. Quehenberger, J. Haybaeck

{"title":"Native Oligodendrocytes in Astrocytomas Might Inhibit Tumor Proliferation by WIF1 Expression","authors":"M. Asslaber, S. Schauer, M. Gogg‐Kamerer, E. Bernhart, F. Quehenberger, J. Haybaeck","doi":"10.1093/jnen/nlw098","DOIUrl":"https://doi.org/10.1093/jnen/nlw098","url":null,"abstract":"Malignant astrocytoma remains incurable and rapidly fatal despite multimodal therapy. In particular, accelerated tumor cell heterogeneity often overcomes therapeutic effects of molecular protein targeting. This study aimed at identifying a gene with therapeutic potential that was consistently downregulated with astrocytoma progression. Analysis of the “Rembrandt” gene expression data revealed Wnt inhibitory factor 1 (WIF1) gene as the most promising candidate with tumor suppressor function. Consequently, 288 randomly selected tissue regions of astrocytoma specimens were investigated immunohistochemically with the aid of image analysis. This in situ approach identified tumor areas with numerous single cells strongly expressing Wif-1. In diffuse and anaplastic astrocytoma, the proliferation index was independent of the generally weak Wif-1 expression in tumor cells but was significantly correlated with the density of Wif-1-expressing single cells, subsequently characterized as native and non-neoplastic oligodendrocytes. Because these cells may contribute to inhibition of tumor cell proliferation by paracrine signaling, the endogenous protein Wif-1 may represent a promising therapeutic agent with expected minimal side effects. Moreover, we suggest that immunohistochemistry for Wif might be useful for discriminating between astrocytic tumors and reactive changes.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89853291","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: 9

Autophagy in Tri-o-cresyl Phosphate-Induced Delayed Neurotoxicity 三邻甲酰磷酸诱导迟发性神经毒性的自噬

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-12-31 DOI: 10.1093/jnen/nlw108

Hai-yang Xu, Pan Wang, Ying-jian Sun, Lu Jiang, Ming-Yuan Xu, Yi-Jun Wu

{"title":"Autophagy in Tri-o-cresyl Phosphate-Induced Delayed Neurotoxicity","authors":"Hai-yang Xu, Pan Wang, Ying-jian Sun, Lu Jiang, Ming-Yuan Xu, Yi-Jun Wu","doi":"10.1093/jnen/nlw108","DOIUrl":"https://doi.org/10.1093/jnen/nlw108","url":null,"abstract":"The widely used organophosphorus compound tri-o-cresyl phosphate (TOCP) elicits delayed neurotoxicity characterized by progressive axonal degeneration in the spinal cord and peripheral nerves. However, the precise mechanisms of TOCP-induced delayed neurotoxicity are not clear. Because autophagy has been linked to the pathogenesis of neurodegenerative diseases, we aimed to characterize autophagy in the progression of TOCP-induced delayed neurotoxicity. In vivo experiments using the adult hen animal model showed that autophagy in spinal cord axons and in sciatic nerves was markedly induced at the early preclinical stage of TOCP-induced delayed neurotoxicity; it was decreased as the delayed neurotoxicity progressed to the overt neuropathy stage. In cultured human neuroblastoma SH-SY5Y cells, TOCP reduced cell growth, and induced prominent autophagy. The autophagy inhibitor 3-methyladenine could attenuate TOCP-induced cytotoxicity, indicating that the autophagy is accountable for TOCP-induced neurotoxicity. In addition, we found that TOCP-induced Parkin translocation to mitochondria in SH-SY5Y cells, suggesting that autophagy may function to degrade mitochondria after TOCP exposure. These results suggest that autophagy may play an important role in the initiation and progression of axonal damage during TOCP-induced neurotoxicity.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82840968","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: 11

OTX2 Defines a Subgroup of Atypical Teratoid Rhabdoid Tumors With Close Relationship to Choroid Plexus Tumors OTX2定义了一个与脉络丛肿瘤密切相关的非典型畸胎瘤样横纹肌样肿瘤亚群

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-12-26 DOI: 10.1093/jnen/nlw101

A. Japp, L. Klein-Hitpass, D. Denkhaus, T. Pietsch

引用次数: 7

Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region 接触蛋白相关蛋白1 (CNTNAP1)突变诱导旁腺区特征性病变

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-12-01 DOI: 10.1093/jnen/nlw093

J. Vallat, M. Nizon, A. Magee, B. Isidor, L. Magy, Y. Péréon, L. Richard, R. Ouvrier, B. Cogné, J. Devaux, S. Zuchner, S. Mathis

{"title":"Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region","authors":"J. Vallat, M. Nizon, A. Magee, B. Isidor, L. Magy, Y. Péréon, L. Richard, R. Ouvrier, B. Cogné, J. Devaux, S. Zuchner, S. Mathis","doi":"10.1093/jnen/nlw093","DOIUrl":"https://doi.org/10.1093/jnen/nlw093","url":null,"abstract":"Congenital hypomyelinating neuropathy is a rare neonatal syndrome responsible for hypotonia and weakness. Nerve microscopic examination shows amyelination or hypomyelination. Recently, mutations in CNTNAP1 have been described in a few patients. CNTNAP1 encodes contactin-associated protein 1 (caspr-1), which is an essential component of the paranodal junctions of the peripheral and central nervous systems, and is necessary for the establishment of transverse bands that stabilize paranodal axo-glial junctions. We present the results of nerve biopsy studies of three patients from two unrelated, non-consanguineous families with compound heterozygous CNTNAP1 mutations. The lesions were identical, characterized by a hypomyelinating process; on electron microscopy, we detected, in all nodes of Ranvier, subtle lesions that have never been previously described in human nerves. Transverse bands of the myelin loops were absent, with a loss of attachment between myelin and the axolemma; elongated Schwann cell processes sometimes dissociated the Schwann cell and axon membranes that bound the space between them. These lesions were observed in the area where caspr-1 is located and are reminiscent of the lesions reported in sciatic nerves of caspr-1 null mice. CNTNAP1 mutations appear to induce characteristic ultrastructural lesions of the paranodal region.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75451856","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: 28

Chronic Traumatic Encephalopathy-Like Abnormalities in a Routine Neuropathology Service 常规神经病理学服务中的慢性创伤性脑病样异常

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-12-01 DOI: 10.1093/jnen/nlw092

S. Noy, S. Krawitz, M. D. Del Bigio

{"title":"Chronic Traumatic Encephalopathy-Like Abnormalities in a Routine Neuropathology Service","authors":"S. Noy, S. Krawitz, M. D. Del Bigio","doi":"10.1093/jnen/nlw092","DOIUrl":"https://doi.org/10.1093/jnen/nlw092","url":null,"abstract":"Chronic traumatic encephalopathy (CTE) has been described mainly in professional athletes and military personnel and is characterized by deposition of hyperphosphorylated tau at the depths of cortical sulci and around blood vessels. To assess CTE-like changes in a routine neuropathology service, we prospectively examined 111 brains (age 18–60 years). The presence of tau-immunoreactive deposits was staged using guidelines described by others and was correlated with the medical history. 72/111 cases were negative for CTE-like changes; 34/111 were CTE stage <1; 3/111 were CTE stage 1; and 2/111 were CTE stage 2. The combined history of head injury and alcohol and/or drug abuse was a significant predictor of any CTE-like changes. Age was also a significant predictor; most with any CTE-like changes were >40 years old. CTE-like changes were not identified at sites of contusion. Among a separate group studied retrospectively, we identified 4 cases that met full criteria for CTE. We conclude that CTE-like findings are not confined to professional athletes; the risk factors of head injury and substance abuse are similar in the routine population. However, the significance of very small hyperphosphorylated tau deposits remains to be determined. In addition, the absence of typical CTE-like deposits near contusion sites keeps open the question of pathogenesis.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90477319","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: 61

New Strategy That Delays Progression of Amyotrophic Lateral Sclerosis in G1H-G93A Transgenic Mice: Oral Administration of Xanthine Oxidoreductase Inhibitors That Are Not Substrates for the Purine Salvage Pathway 延缓G1H-G93A转基因小鼠肌萎缩性侧索硬化症进展的新策略:口服不是嘌呤回收途径底物的黄嘌呤氧化还原酶抑制剂

Journal of Neuropathology & Experimental Neurology Pub Date : 2016-12-01 DOI: 10.1093/jnen/nlw088

S. Kato, Masako Kato, Teruo Kusano, T. Nishino

{"title":"New Strategy That Delays Progression of Amyotrophic Lateral Sclerosis in G1H-G93A Transgenic Mice: Oral Administration of Xanthine Oxidoreductase Inhibitors That Are Not Substrates for the Purine Salvage Pathway","authors":"S. Kato, Masako Kato, Teruo Kusano, T. Nishino","doi":"10.1093/jnen/nlw088","DOIUrl":"https://doi.org/10.1093/jnen/nlw088","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS), Lou Gehrig’s disease, is a progressive fatal neurodegenerative disease that involves both upper and lower motor neurons. We orally administered 4 xanthine oxidoreductase (XOR) inhibitors to G1H-G93A mice carrying 25 transgene copy numbers of human mutant G93A superoxide dismutase 1, from 80 days of age. Three nonpurine-analogue inhibitors (TEI-6720: Febuxostat, Y-700 and FYX-051), but not allopurinol with a purine analogue ring (pyrazolo pyrimidine ring), significantly delayed disease onset, prolonged survival and the duration of disease stages, improved clinical signs, and alleviated weight loss. Exercise testing (extension reflex, inclined plane, footprint, rotarod, and beam balance tests) showed significantly improved motor function in the G1H-G93A mice treated with these 3 inhibitors. Significant amelioration of disease was seen even when TEI-6720 or Y-700 was administered after the appearance of early signs. Histopathological evaluation in the late stage revealed that G1H-G93A mice treated with TEI-6720 had well-preserved motor neurons and fewer inclusion bodies, compared with mice treated with placebo or with allopurinol. Our results indicate that these 3 nonpurine-analogue XOR inhibitors might increase the supply of high-energy compounds via the purine salvage pathway, thereby protecting motor neurons against death. This strategy may be applicable for oral therapy of ALS patients.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89107990","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: 13