Journal of Huntington's disease最新文献_第2页

Special issue: Glia and non-neuronal cells in Huntington's disease. 特刊：亨廷顿病中的神经胶质细胞和非神经元细胞。

IF 3.1

Journal of Huntington's disease Pub Date : 2025-08-01 Epub Date: 2025-08-07 DOI: 10.1177/18796397251358289

Mahmoud A Pouladi, Asa Petersen

引用次数: 0

The role of oligodendroglial dysfunction in Huntington's disease. 少突胶质功能障碍在亨廷顿病中的作用。

IF 3.1

Journal of Huntington's disease Pub Date : 2025-08-01 Epub Date: 2025-08-07 DOI: 10.1177/18796397251358017

Xinhui Li, Shihua Li, Xiao-Jiang Li, Huu Phuc Nguyen, Asa Petersen, Mahmoud A Pouladi

{"title":"The role of oligodendroglial dysfunction in Huntington's disease.","authors":"Xinhui Li, Shihua Li, Xiao-Jiang Li, Huu Phuc Nguyen, Asa Petersen, Mahmoud A Pouladi","doi":"10.1177/18796397251358017","DOIUrl":"10.1177/18796397251358017","url":null,"abstract":"Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms. Research efforts to understand and treat the disease have historically focused on neuronal pathology, but growing evidence underscores the critical role of oligodendrocytes in its pathogenesis. This review synthesizes recent findings on oligodendroglial dysfunction in HD, showing that white matter abnormalities arise early in disease progression, often preceding gray matter changes and clinical symptoms. Neuroimaging and postmortem studies reveal significant white matter atrophy, myelin breakdown, and impaired oligodendrocyte maturation in both patients and animal models. The myelination response to environmental factors is also altered in HD, suggesting impaired white matter plasticity in the disease. At the molecular level, mutant huntingtin disrupts oligodendrocyte function through transcriptional dysregulation of myelin genes, epigenetic modifications involving PRC2 and REST, altered lipid metabolism, thiamine pathway dysfunction, and aberrant BDNF signaling. Key oligodendroglial transcriptional regulators such as MYRF and TCF7L2 are compromised in HD, leading to defective myelination and reduced metabolic support for neurons. Recognizing the role of these mechanisms provides potential biomarkers for early detection and therapeutic targets aimed at preserving both neuronal and glial function in HD.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"14 3","pages":"270-278"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794618","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

Emerging roles of microglia and neuroinflammation in Huntington's disease: From pathophysiology to clinical trials. 小胶质细胞和神经炎症在亨廷顿病中的新作用：从病理生理学到临床试验。

IF 3.1

Journal of Huntington's disease Pub Date : 2025-08-01 Epub Date: 2025-03-28 DOI: 10.1177/18796397251330144

Muna Abedrabbo, Pardis Kazemian, Colúm Connolly, Blair R Leavitt

{"title":"Emerging roles of microglia and neuroinflammation in Huntington's disease: From pathophysiology to clinical trials.","authors":"Muna Abedrabbo, Pardis Kazemian, Colúm Connolly, Blair R Leavitt","doi":"10.1177/18796397251330144","DOIUrl":"10.1177/18796397251330144","url":null,"abstract":"Microglia, the resident immune cells of the central nervous system, play a pivotal role in the response to Huntington's disease (HD) pathology. Through both cell-autonomous mechanisms and exposure to external pathogenic stimuli, microglia transition from a resting to an activated state, producing pro-inflammatory cytokines and chemokines that mediate inflammation. While this inflammatory response attempts to have a neuroprotective compensatory effect, chronic microglial activation exacerbates neuroinflammation, neurodegeneration and contributes to disease progression. Evidence from postmortem analyses and neuroimaging studies indicates that activated microglia are present in various stages of HD, correlating with neuronal degeneration and clinical symptoms. Enhanced microglial activation has been identified as an early predictor of disease onset, particularly in premanifest HD, highlighting the potential of targeting microglial pathways for therapeutic interventions. This review explores microglia's dual role in HD pathophysiology, exploring their contributions to both neuroinflammation and neuroprotection. It also examines recent advances in clinical trials aimed at modulating microglial activity, paving the way for novel therapeutic strategies to alter disease progression and improve patient outcomes.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"241-257"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730320","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

Dysregulated astrocyte cholesterol synthesis in Huntington's disease: A potential intersection with other cellular dysfunctions. 亨廷顿病星形胶质细胞胆固醇合成失调：与其他细胞功能障碍的潜在交叉

IF 3.1

Journal of Huntington's disease Pub Date : 2025-08-01 Epub Date: 2025-05-21 DOI: 10.1177/18796397251336192

Marta Valenza

{"title":"Dysregulated astrocyte cholesterol synthesis in Huntington's disease: A potential intersection with other cellular dysfunctions.","authors":"Marta Valenza","doi":"10.1177/18796397251336192","DOIUrl":"10.1177/18796397251336192","url":null,"abstract":"Astrocytes are key elements for synapse development and function. Several astrocytic dysfunctions contribute to the pathophysiology of various neurodegenerative disorders, including Huntington's disease (HD), an autosomal-dominant neurodegenerative disorder that is characterized by motor and cognitive defects with behavioral/psychiatric disturbances. One dysfunction in HD related to astrocytes is reduced cholesterol synthesis, leading to a decreased availability of local cholesterol for synaptic activity. This review describes the specific role of astrocytes in the brain local cholesterol synthesis and presents evidence supporting a defective astrocyte-neuron cholesterol crosstalk in HD, by focusing on SREBP-2, the transcription factor that regulates the majority of genes involved in the cholesterol biosynthetic pathway. The emerging coordination of SREBP-2 with other physiological processes, such as energy metabolism, autophagy, and Sonic Hedgehog signaling, is also discussed. Finally, this review intends to stimulate future research directions to explore whether the impairment of astrocytic SREBP-2-mediated cholesterol synthesis in HD associates with other cellular dysfunctions in the disease.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"229-240"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110099","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

Neuroinflammation in Huntington's disease: Causes, consequences, and treatment strategies. 亨廷顿氏病的神经炎症：原因、后果和治疗策略。

IF 3.1

Journal of Huntington's disease Pub Date : 2025-08-01 Epub Date: 2025-08-07 DOI: 10.1177/18796397251338207

Alina Blusch, Maria Björkqvist

{"title":"Neuroinflammation in Huntington's disease: Causes, consequences, and treatment strategies.","authors":"Alina Blusch, Maria Björkqvist","doi":"10.1177/18796397251338207","DOIUrl":"10.1177/18796397251338207","url":null,"abstract":"Huntington's disease (HD) is a progressive neurodegenerative disorder, and increasing evidence suggests that inflammation, both central and peripheral, plays a role in disease progression. Neurohistology and neuroimaging studies illustrate neuroinflammatory processes as part of HD pathophysiology. Furthermore, studies of blood and cerebrospinal fluid from HD patients show altered levels of inflammatory markers and immune cell populations that could influence neuroinflammation and the neurodegenerative process. Here, we review findings contributing to our understanding of the significance of immune activation in HD pathology. We discuss evidence of intrinsic effects of mutant huntingtin within immune cells and central immune alterations that contribute to neuroinflammation and neurodegeneration. We address the roles of central immune cells, as well as the potential contributions of peripheral signals and cell types in HD immune activation. We further discuss opportunities and challenges in utilizing immune-modulation strategies for future treatment approaches. A better understanding of neuroimmune interactions in HD can provide insights for manipulating these responses, potentially facilitating the development of therapies aimed at reducing the impact of neuroinflammatory and degenerative processes.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"14 3","pages":"258-269"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794614","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

The glymphatic system in Huntington's disease. 亨廷顿氏病的淋巴系统。

IF 3.1

Journal of Huntington's disease Pub Date : 2025-08-01 Epub Date: 2025-03-28 DOI: 10.1177/18796397251331436

Wenzhen Duan, Yuan Zhou, Hongshuai Liu

{"title":"The glymphatic system in Huntington's disease.","authors":"Wenzhen Duan, Yuan Zhou, Hongshuai Liu","doi":"10.1177/18796397251331436","DOIUrl":"10.1177/18796397251331436","url":null,"abstract":"The glymphatic system, a macroscopic waste clearance network in the brain, plays a vital role in maintaining neuronal health and brain homeostasis. Functionally analogous to the lymphatic system in other organs, the term \"glymphatic\" combines \"glial\" and \"lymphatic.\" This system facilitates the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) in the parenchyma, aiding in the removal of soluble proteins and metabolites while distributing essential nutrients and signaling molecules. Its functionality is closely tied to aquaporin 4 (AQP4) water channels, located primarily on astrocytic endfeet, which mediate water movement between the CSF and ISF. Proper glymphatic function relies on the cellular distribution of AQP4 channels and its astroglial endfeet polarization. Emerging evidence links glymphatic dysfunction to several neurodegenerative disorders, including Huntington's disease (HD). Understanding the role of the glymphatic system in HD pathogenesis could provide novel insights into disease pathogenesis and new therapeutic approaches. This review examines the connection between glymphatic dysfunction and HD, highlighting future research directions and therapeutic advancement for HD. It explores pharmacological interventions and lifestyle modifications aimed at optimizing glymphatic function to improve HD management.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"279-290"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12331436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730393","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

Dysregulation of huntingtin interacting protein networks in human juvenile Huntington's disease brain. 人类青少年亨廷顿病大脑中亨廷顿蛋白相互作用蛋白网络的失调。

IF 2.1

Journal of Huntington's disease Pub Date : 2025-07-23 DOI: 10.1177/18796397251358348

Sonia Podvin, Brin Rosenthal, Charles Mosier, Enlin Wei, Kathleen M Fisch, Vivian Hook

{"title":"Dysregulation of huntingtin interacting protein networks in human juvenile Huntington's disease brain.","authors":"Sonia Podvin, Brin Rosenthal, Charles Mosier, Enlin Wei, Kathleen M Fisch, Vivian Hook","doi":"10.1177/18796397251358348","DOIUrl":"https://doi.org/10.1177/18796397251358348","url":null,"abstract":"BackgroundHuman Huntington's disease (HD) is a genetic neurodegenerative disorder caused by the mutant HTT gene containing CAG repeat expansions, resulting in motor dysfunction and behavioral deficits. CAG repeats of 40-53 occur in adult HD and 60-120 repeats occur in early onset juvenile HD, differing from the normal range of 5-35 repeats.ObjectiveThe HTT gene is translated to the huntingtin (HTT) protein that interacts with proteins in the development of HD. There have been few studies of HTT protein interactors in human HD brain. Therefore, this study evaluated the hypothesis that dysregulation of HTT protein interactors occurs in human juvenile HD brains.MethodsThe strategy of this study was to analyze proteomic data of human juvenile HD brain putamen and cortex regions for dysregulation of HTT interacting proteins, using a database that we compiled of HTT interactors identified in HD model systems from yeast to HD mice.ResultsResults showed significant dysregulation of HTT protein interactors of mitochondria, signal transduction, RNA splicing, chromatin organization, translation, membrane trafficking, endocytosis, vesicle, protein modification, granule membrane, and macroautophagy pathways. The majority of downregulated and upregulated HTT interactors occurred in the putamen region compared to cortex. Dysregulation displayed downregulation of mitochondria and signal transduction interactors, combined with upregulation of RNA splicing, chromatin organization, and translational interactors. Network analysis revealed interactions among clusters of HTT interactors.ConclusionsThese findings demonstrate prevalent dysregulation of HTT protein interactors in human juvenile HD brain, especially in the putamen region that controls movement deficits in HD.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251358348"},"PeriodicalIF":2.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698656","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

Reliability and validity of the Huntington's Disease Everyday Functioning (Hi-DEF): A patient-reported measure of cognitive capacity on daily functioning in Huntington's disease. 亨廷顿氏病日常功能（Hi-DEF）的可靠性和有效性：亨廷顿氏病患者报告的日常功能认知能力测量。

IF 2.1

Journal of Huntington's disease Pub Date : 2025-07-22 DOI: 10.1177/18796397251358375

Jennifer Petrillo, Ruta Sawant, Rebecca Rogers, Sophie Cleanthous, Stefan Cano, Rajeev Kumar, Jennifer Klapper, Luis A Sierra, Jee Bang, Karen Elta Anderson, Deborah A Hall, Susan Perlman, Henry Moore, Danny Bega, Jason Johannesen, Emma Elliott

{"title":"Reliability and validity of the Huntington's Disease Everyday Functioning (Hi-DEF): A patient-reported measure of cognitive capacity on daily functioning in Huntington's disease.","authors":"Jennifer Petrillo, Ruta Sawant, Rebecca Rogers, Sophie Cleanthous, Stefan Cano, Rajeev Kumar, Jennifer Klapper, Luis A Sierra, Jee Bang, Karen Elta Anderson, Deborah A Hall, Susan Perlman, Henry Moore, Danny Bega, Jason Johannesen, Emma Elliott","doi":"10.1177/18796397251358375","DOIUrl":"https://doi.org/10.1177/18796397251358375","url":null,"abstract":"BackgroundThe Huntington's Disease (HD) Everyday Functioning (Hi-DEF) is a novel patient-reported outcome (PRO) scale developed to assess the impact of cognitive impairment on daily functioning in early HD patients.ObjectiveTo examine the psychometric properties, including reliability and validity, of the Hi-DEF. Findings from psychometric analyses using classical test theory (CTT) approach are presented here.MethodsA non-interventional validation study was conducted across nine HD Centers of Excellence across the US.ResultsPatients with HD (n = 151) were recruited: 59% were female, mean (SD) age was 47 (12) years, and mean (range) Total Functional Capacity (TFC) score was 11.4 (8-13). Excellent internal consistency reliability was observed for the Hi-DEF scale total score (Cronbach's alpha: 0.98) and across subscales (alpha range 0.87-0.96). Most targeting and scaling assumptions were met, although there were ceiling effects for three subscales. Construct validity was demonstrated by moderate to high Spearman's rank-order correlations with TFC scores (range r = -0.38 to -0.62) and known and validated measures such as the HD-PRO-TRIADTM (range r = 0.75-0.90), and ability to discriminate between levels of functional impairment (TFC 13, 12-11, and 10-8; p < 0.001). Correlations with Cambridge Neuropsychological Test Automated Battery (CANTAB) cognitive performance measures were low to moderate and ranged from 0.06 to 0.38.ConclusionsThe Hi-DEF is a reliable and valid PRO scale measuring the impact of cognitive impairment on daily functioning, assessing facets of cognitive functioning in context of activities of daily living impacted in early stages of HD.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251358375"},"PeriodicalIF":2.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682720","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

Epidemiology and clinical features of Huntington's disease in MENASA region: A systematic review and meta-analysis. MENASA地区亨廷顿舞蹈病的流行病学和临床特征：系统回顾和荟萃分析。

IF 2.1

Journal of Huntington's disease Pub Date : 2025-07-03 DOI: 10.1177/18796397251356620

Mehri Salari, Kamran Rezaei, Fatemeh Hojjati Pour, Mercedeh Sepehrnia, Masoud Etemadifar

{"title":"Epidemiology and clinical features of Huntington's disease in MENASA region: A systematic review and meta-analysis.","authors":"Mehri Salari, Kamran Rezaei, Fatemeh Hojjati Pour, Mercedeh Sepehrnia, Masoud Etemadifar","doi":"10.1177/18796397251356620","DOIUrl":"https://doi.org/10.1177/18796397251356620","url":null,"abstract":"BackgroundGiven the scarcity of comprehensive data on Huntington's disease in many Asian and African countries, it is more effective to focus on specific regions where there is a significant concentration of available data.ObjectiveThis study decided to evaluate the epidemiology and features of Huntington's disease in countries of the Middle East, North Africa, and South Asia (MENASA) regions.MethodsIn this meta-analysis, the limited maximum likelihood (REML) approach was applied to the estimated point prevalence mentioned in original studies of each MENASA country. Additionally, research on Huntington's disease characteristics in each nation was utilized to give a general picture of the disease's status in those nations.ResultsThe pooled point prevalence estimation of the prevalence studies was 8.64 per 100,000 (95% CI, -0.04-17.33; I2 = 100%). Among 14 cohort and cross-sectional studies on individuals with Huntington's disease in the MENASA region, 5.61% of the patients had juvenile-onset Huntington's disease, and 2.3% had late-onset Huntington's disease. In addition, 68.58%, 17.82%, and 45.17% of the individuals were reported with motor symptoms at the onset, abnormal cognitive assessment scores, and degrees of psychological disturbance, respectively. The mean age at onset was 44.85 years, and the mean number of pathologic CAG repeats was 45.46.ConclusionsNotable differences in the frequency of symptoms of onset and pooled prevalence of HD in the MENASA region probably address a serious lack of sufficient information. The results would help clinicians and governments develop public health strategies, and further research could be conducted on these results.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251356620"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553753","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}

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Huntington disease and Beta-blocker drug use. 亨廷顿病和受体阻滞剂药物的使用。

IF 2.1

Journal of Huntington's disease Pub Date : 2025-06-27 DOI: 10.1177/18796397251352042

Peter A LeWitt, Bisena Bulica

引用次数: 0