Neurology International最新文献

{"title":"Anti-Calcitonin Gene-Related Peptide Monoclonal Antibody Is Effective for Preventing Migraine Aura Without Headache.","authors":"Yasushi Shibata","doi":"10.3390/neurolint16060097","DOIUrl":"10.3390/neurolint16060097","url":null,"abstract":"<p><strong>Background: </strong>Anti-calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are clinically effective in preventing the migraine attacks, photophobia, and migraine auras associated with headaches. However, no study has yet investigated the effectiveness of CGRP mAbs in preventing migraine aura without headache.</p><p><strong>Case report: </strong>A female patient of 49 years old presented with a long history (since age 10) of photosensitivity and typical migraine auras without a headache. The symptoms slightly responded to oral medication, lomerizine chloride, but did not completely resolve. Just one day after the administration of galcanezumab, her photo-hypersensitivity and migraine aura had completely resolved. Consequently, the administration of the oral migraine preventive medication was discontinued. Monthly galcanezumab at a dose of 120 mg was continuously given and she did not re-experience any auras or headaches.</p><p><strong>Conclusions: </strong>The use of CGRP mAbs can be considered as a potential treatment in preventing migraine aura without headache. Currently, CGRP mAb is indicated only for migraines with and without auras. Given our findings and the promising effects of this medication for this migraine subtype, a large clinical trial is required to better assess the effects and potential adverse events of CGRP mAb in patients with migraine aura without headache.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1279-1284"},"PeriodicalIF":3.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710647","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}

{"title":"Efficacy of Nusinersen Treatment in Type 1, 2, and 3 Spinal Muscular Atrophy: Real-World Data from a Single-Center Study.","authors":"Anna Lemska, Piotr Ruminski, Jakub Szymarek, Sylwia Studzinska, Maria Mazurkiewicz-Beldzinska","doi":"10.3390/neurolint16060096","DOIUrl":"10.3390/neurolint16060096","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is an inherited neuromuscular disease characterized by progressive muscle weakness and atrophy due to the absence of the survival motor neuron 1 (<i>SMN1</i>) gene. SMA is classified into types 0 through 4 based on the age of symptom onset and the severity of motor function decline. Recent advances in SMA treatment, including nusinersen, onasemnogene abeparvovec, and risdiplam, have significantly improved the prognosis of SMA patients. This study evaluated the safety and efficacy of nusinersen in pediatric patients with SMA types 1, 2, and 3 in a real-world clinical setting.</p><p><strong>Methods: </strong>This prospective observational single-center study assessed the treatment effects of nusinersen in 23 pediatric patients with genetically confirmed SMA over a 22-month observation period. All the participants received intrathecal loading doses of 12 mg of nusinersen on days 1, 14, 28, and 63, followed by maintenance doses every four months. Functional assessments were conducted using the CHOP-INTEND scale. Data were collected during routine patient visits, including clinical laboratory tests and vital sign parameters, and adverse events were recorded. The inclusion criteria were defined by the national reimbursement program for nusinersen treatment in Poland.</p><p><strong>Results: </strong>Initially, 37 patients ranging from 1 month old to 18 years old were included, but 23 were ultimately observed due to changes in treatment regimens or assessment scales. The patients showed significantly improved CHOP-INTEND scores over the 22-month period. At 6 months, the average increase was 4.2 points, continuing to 17.8 points at 22 months. By the end of the study, 100% of patients showed either stabilization or improvement, with significant clinical improvements observed in several patients. Nusinersen was generally well-tolerated, with post-lumbar puncture headache and lower back pain being the most common adverse events.</p><p><strong>Conclusions: </strong>Nusinersen treatment significantly enhances motor function in pediatric patients with SMA types 1, 2, and 3. This study demonstrates the importance of early and sustained treatment, with most patients showing the continuous improvement or stabilization of motor function. These findings support the use of nusinersen as an effective therapy for SMA; however, further research is needed to understand the long-term outcomes and optimize treatment strategies.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1266-1278"},"PeriodicalIF":3.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710705","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}

{"title":"Explainable Machine Learning Models for Brain Diseases: Insights from a Systematic Review.","authors":"Mirko Jerber Rodríguez Mallma, Luis Zuloaga-Rotta, Rubén Borja-Rosales, Josef Renato Rodríguez Mallma, Marcos Vilca-Aguilar, María Salas-Ojeda, David Mauricio","doi":"10.3390/neurolint16060098","DOIUrl":"10.3390/neurolint16060098","url":null,"abstract":"<p><p>In recent years, Artificial Intelligence (AI) methods, specifically Machine Learning (ML) models, have been providing outstanding results in different areas of knowledge, with the health area being one of its most impactful fields of application. However, to be applied reliably, these models must provide users with clear, simple, and transparent explanations about the medical decision-making process. This systematic review aims to investigate the use and application of explainability in ML models used in brain disease studies. A systematic search was conducted in three major bibliographic databases, Web of Science, Scopus, and PubMed, from January 2014 to December 2023. A total of 133 relevant studies were identified and analyzed out of a total of 682 found in the initial search, in which the explainability of ML models in the medical context was studied, identifying 11 ML models and 12 explainability techniques applied in the study of 20 brain diseases.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1285-1307"},"PeriodicalIF":3.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710751","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}

{"title":"The Role of Greek Olive Leaf Extract in Patients with Mild Alzheimer's Disease (the GOLDEN Study): A Randomized Controlled Clinical Trial.","authors":"Sofia Loukou, Georgia Papantoniou, Anastasia Pantazaki, Magdalini Tsolaki","doi":"10.3390/neurolint16060095","DOIUrl":"10.3390/neurolint16060095","url":null,"abstract":"<p><p><b>Background</b>: Olive leaves are a significant source of biophenols, which have a beneficial impact on cognitive performance. <b>Objective</b>: To examine, for the first time, in humans the effect of the daily consumption of a beverage containing olive leaf extract (OLE) versus a Mediterranean diet (MeDi) on patients diagnosed with mild Alzheimer's Disease (AD), in addition to their regular treatment. <b>Methods</b>: A randomized clinical trial compared OLE's effects on cognitive and functional performance in 55 mild AD patients. Each participant was randomly assigned to two groups: (1) Group 1 was given olive leaves for making a daily beverage and MeDi instructions through monthly diet programs; (2) Group 2 received only the MeDi instructions. After six months, all participants underwent a second neuropsychological evaluation. <b>Results</b>: Group 1 participants had statistically significantly higher MMSE scores compared to Group 2 with a <i>p</i>-value of 0.0135. Specifically, the mean MMSE difference in patients receiving OLE was close to 0, indicating no memory deterioration, whereas in controls it was -4.1, indicative of cognitive decline. The remaining neuropsychological assessments (FRSSD, FUCAS, ADAS-Cog, CDR, GDS, and NPI) revealed better results in the OLE group, except for GDS, which showed no change, but without statistically significant differences between the two groups.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1247-1265"},"PeriodicalIF":3.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710445","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}

{"title":"Combining Transcranial Direct Current Stimulation with Exercise to Improve Mobility, Stability, and Tremor Management in 25 Individuals with Parkinson's Disease.","authors":"Fabrício D de Almeida, Yiyu Wang, Rodrigo C de Mello Pedreiro, Ana Carolina B Brizzi, Shirley F Campos, Melina P Sales, Deanna M Kennedy, Osmar Pinto Neto","doi":"10.3390/neurolint16060093","DOIUrl":"10.3390/neurolint16060093","url":null,"abstract":"<p><strong>Background/objectives: </strong>Parkinson's disease (PD) is a neurodegenerative disorder characterized by tremors, balance impairments, and mobility limitations. Innovative approaches like combining transcranial direct current stimulation (tDCS) with exercise show promise in addressing these symptoms. This study investigates the effects of exercise combined with tDCS on mobility and tremor management in PD patients.</p><p><strong>Methods: </strong>Twenty-five individuals aged 60-75 (66.6 ± 7.33), diagnosed with PD (Hoehn and Yahr stage 2-3), were assigned to three groups in a randomized controlled design: exercise with active tDCS (<i>n</i> = 8), exercise with sham tDCS (<i>n</i> = 8), and a control group (<i>n</i> = 9). Dual-task training sessions focusing on walking speed, balance, and force control were conducted over ten sessions.</p><p><strong>Results: </strong>No significant differences were detected across the groups for grip strength or force control measures (<i>p</i> > 0.05). Significant improvements were observed in the intervention group: the Timed Up and Go (TUG) test showed a significant reduction in time (mean difference = 2.498 s, <i>p</i> < 0.001, ηp² = 0.331); anterior-posterior displacement significantly increased (mean difference = 21.375 mm, <i>p</i> = 0.0269, ηp² = 0.303); and force-tremor decoupling improved, with coherence in the 1-4 Hz band significantly decreasing (<i>p</i> = 0.0067). Finally, changes in TUG from post- to pre-treatment values were significantly positively correlated with the changes in coherence (R = 0.468, <i>p</i> = 0.018).</p><p><strong>Conclusions: </strong>Combining tDCS with exercise enhances mobility and tremor management in PD patients. These findings support the potential for such interventions to improve functional outcomes and quality of life for individuals with PD.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1223-1238"},"PeriodicalIF":3.2,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710675","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}

{"title":"Functional Outcomes After Decompressive Surgery in Patients with Malignant Space-Occupying Cerebellar Infarction.","authors":"Enayatullah Baki, Lea Baumgart, Victoria Kehl, Felix Hess, Andreas Wolfgang Wolff, Arthur Wagner, Moritz Roman Hernandez Petzsche, Tobias Boeckh-Behrens, Bernhard Hemmer, Bernhard Meyer, Jens Gempt, Silke Wunderlich","doi":"10.3390/neurolint16060094","DOIUrl":"10.3390/neurolint16060094","url":null,"abstract":"<p><p><b>Background and Purpose</b>: Decompressive surgery is a potentially life-saving treatment in patients with malignant space-occupying cerebellar infarction. However, there is only limited literature on functional outcomes and complications after surgery. Our aim was to establish markers which predict poor outcome. <b>Methods</b>: We retrospectively analyzed data of all patients who underwent surgery due to malignant swelling of a space-occupying cerebellar infarction in our hospital between 2005 and 2023. Statistical analyses were conducted on multiple parameters to identify predictors of poor functional outcome (mRS 4-6) 90 days after surgery. Complications during hospitalization were reviewed for each patient. <b>Results</b>: In total, 58 patients received decompressive surgery. The 90-day mortality rate was 27.6% (n = 16). A good functional outcome (mRS 0-3) 90 days after surgery was achieved in 24 patients (41.4%). Multivariable analysis revealed multiple factors associated with a poor outcome on day 90 (mRS 4-6): a higher premorbid mRS score (OR 2.715 [95% CI, 1.166-6.323]; <i>p</i> = 0.021), higher NIHSS score on admission (OR 1.088 [95% CI, 1.014, 1.168]; <i>p</i> = 0.019) and the presence of an additional brainstem infarction (OR 7.035, [95% CI, 1.255, 39.424], <i>p</i> = 0.027). Hyperactive delirium was associated with good clinical outcome (OR 0.020 [95%CI, 0.001-0.623]; <i>p</i> = 0.026). Aspiration pneumonia (n = 22, 37.9%), urinary tract infection (n = 15, 25.9%), and hyperactive delirium (n = 8, 13.8%) were the most common complications during hospitalization. <b>Conclusions</b>: Decompressive surgery is a safe, life-saving treatment for malignant space-occupying cerebellar infarction. Higher premorbid mRS, higher NIHSS score on admission and the presence of brainstem infarction are associated with a poor functional outcome.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1239-1246"},"PeriodicalIF":3.2,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710752","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}

{"title":"Ketogenic Diet Improves Sleep Quality and Daytime Sleepiness in Chronic Migraine: A Pilot Study.","authors":"Yan Tereshko, Simone Dal Bello, Enrico Belgrado, Cherubino Di Lorenzo, Alice Pittino, Francesca Filippi, Francesca Valdemarin, Christian Lettieri, Gian Luigi Gigli, Annacarmen Nilo, Gaia Pellitteri, Giovanni Merlino, Mariarosaria Valente","doi":"10.3390/neurolint16060091","DOIUrl":"10.3390/neurolint16060091","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study is to assess the sleep quality and daytime sleepiness improvement in chronic migraineurs after 6 months of a 2:1 KD (ketogenic diet) and LGID (low-glycemic-index diet).</p><p><strong>Methods: </strong>Twenty-six patients underwent 2:1 KD (11 patients) and LGID (15 patients). PSQI (Pittsburgh sleep quality index) and ESS (Epworth sleepiness scale) were administered at the baseline and the 3-month and 6-month follow-up. MIDAS (Migraine Disability Assessment), HIT-6 (Headache Impact Test 6), migraine frequency (migraine days per month), migraine intensity, BMI (Body Mass Index), FM (Fat Mass), and FFM (Fat-Free Mass) were also assessed.</p><p><strong>Results: </strong>PSQI (F_{1.544, 38.606} = 7.250; <i>p</i> = 0.004), ESS (F_{1.988, 49.708} = 9.938; <i>p</i> < 0.001), HIT-6 (F_{1.432, 35.805} = 12.693; <i>p</i> < 0.001), migraine frequency (F_{1.522, 38.041} = 23.070; <i>p</i> < 0.001), migraine intensity (F_{1.949, 48.721} = 18.798; <i>p</i> < 0.001), BMI (F_{1.274, 31.857} = 38.191; <i>p</i> < 0.001), and FM (F_{1.245, 31.134} = 45.487; <i>p</i> < 0.001) improved significantly. The MIDAS (F_{1.005, 25.121} = 3.037; <i>p</i> = 0.093) and the FMM (F_{1.311, 32.784} = 1.741; <i>p</i> = 0.197) did not improve significantly. The ESS (<i>p</i> = 0.712) and PSQI (<i>p</i> = 0.776) data at 3-month and 6-month follow-ups did not differ significantly, as well as for migraine frequency, migraine intensity, BMI, FM, and HIT-6. A mild correlation emerged between the mean FM and mean ESS reduction during the 6 months (<i>r</i> = 0.497, <i>p</i> = 0.010).</p><p><strong>Conclusions: </strong>Six months of LGID and 2:1 KD can improve sleep quality and daytime sleepiness in patients with chronic migraine. The effectiveness on migraine, sleep quality, and daytime sleepiness does not differ significantly between the 3-month and 6-month follow-up periods.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1203-1213"},"PeriodicalIF":3.2,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710754","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}

{"title":"Chronic Immune Sensory Polyradiculopathy (CISP): A Systematic Review of the Literature.","authors":"Saurabh Singhal, Rahul Khanna, Anudeep Surendranath, Jayksh Chhabra, Vismay Thakkar, Rajesh Gupta","doi":"10.3390/neurolint16060092","DOIUrl":"10.3390/neurolint16060092","url":null,"abstract":"<p><p>Chronic immune sensory polyradiculopathy (CISP) is a rare inflammatory immune disorder affecting the nervous system, primarily targeting the proximal sensory nerve roots. The condition was first described by Sinreich in 2004. We conducted a systematic review of CISP cases published on PubMed to identify common clinical presentations, along with neurophysiological, radiological, cerebrospinal fluid (CSF), and other findings. Our review included a total of 22 patients from 8 articles. Many patients presented with gait difficulties and sensory ataxia and were found to have normal nerve conduction studies (NCS) and electromyography (EMG) but exhibited characteristic abnormalities in somatosensory evoked potentials (SSEP), elevated CSF protein levels, thickened nerve roots on contrast-enhanced lumbar spine MRIs, and histological changes on nerve root biopsies. Clinical improvement was observed following treatment with steroids and/or intravenous immunoglobulin (IVIG). The study concluded that while CISP is rare, it is an important clinical entity to consider, as accurate diagnosis and appropriate treatment can lead to significant improvements in neurological symptoms and disabilities.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1214-1222"},"PeriodicalIF":3.2,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710674","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}

{"title":"Bridging the Gap: Improving Acute Ischemic Stroke Outcomes with Intravenous Thrombolysis Prior to Mechanical Thrombectomy.","authors":"Jessica Seetge, Balázs Cséke, Zsófia Nozomi Karádi, Edit Bosnyák, László Szapáry","doi":"10.3390/neurolint16060090","DOIUrl":"https://doi.org/10.3390/neurolint16060090","url":null,"abstract":"<p><strong>Background/objectives: </strong>Current guidelines recommend intravenous thrombolysis (IVT) followed by mechanical thrombectomy (MT) for patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). This combined approach, known as bridging therapy (BT), is believed to increase the likelihood of a favorable functional outcome when administered within 4.5 h of symptom onset. However, the benefits of BT over direct mechanical thrombectomy (d-MT) remain debated. This study aimed to compare the outcomes of AIS-LVO patients undergoing MT within 6 h of symptom onset, with and without prior IVT.</p><p><strong>Methods: </strong>Within the prospective Transzlációs Idegtudományi Nemzeti Laboratórium (TINL) STROKE-registry, AIS-LVO patients admitted to the Department of Neurology, University of Pécs between February 2023 and June 2024 were investigated. The primary endpoint was the proportion of patients reaching functional independence at 90 days, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary endpoints included clinical improvement at 72 h (National Institute of Health Stroke Scale [NIHSS] score of ≤1 or a change from baseline [ΔNIHSS] of ≥4) and successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] score ≥ 2). Safety outcomes were evaluated based on thrombus migration and intracranial hemorrhage (ICH). Results were compared using linear and logistic regression analyses adjusted for baseline variables.</p><p><strong>Results: </strong>Of 82 patients, 51 (62.2%) received BT, while 31 (37.8%) underwent d-MT. The BT group showed a significantly higher rate of functional independence (45.7% vs. 17.2%, <i>p</i> = 0.014) and a lower 90-day mortality rate (13.7% vs. 35.5%, <i>p</i> = 0.029). Multivariate analysis revealed that IVT was independently associated with favorable functional outcomes (<i>p</i> = 0.011) and reduced mortality (<i>p</i> = 0.021). No significant differences were observed in terms of clinical improvement at 72 h, successful recanalization, thrombus migration, or hemorrhagic transformation between the groups.</p><p><strong>Conclusions: </strong>This study supports current guidelines recommending BT for thrombectomy-eligible AIS-LVO patients, offering new insights into the ongoing clinical debate.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1189-1202"},"PeriodicalIF":3.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504822","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}

{"title":"UBL3 Interacts with PolyQ-Expanded Huntingtin Fragments and Modifies Their Intracellular Sorting.","authors":"Soho Oyama, Hengsen Zhang, Rafia Ferdous, Yuna Tomochika, Bin Chen, Shuyun Jiang, Md Shoriful Islam, Md Mahmudul Hasan, Qing Zhai, A S M Waliullah, Yashuang Ping, Jing Yan, Mst Afsana Mimi, Chi Zhang, Shuhei Aramaki, Yusuke Takanashi, Tomoaki Kahyo, Yoshio Hashizume, Daita Kaneda, Mitsutoshi Setou","doi":"10.3390/neurolint16060089","DOIUrl":"https://doi.org/10.3390/neurolint16060089","url":null,"abstract":"<p><strong>Background/objectives: </strong>UBL3 (Ubiquitin-like 3) is a protein that plays a crucial role in post-translational modifications, particularly in regulating protein transport within small extracellular vesicles. While previous research has predominantly focused on its interactions with α-synuclein, this study investigates UBL3's role in Huntington's disease (HD). HD is characterized by movement disorders and cognitive impairments, with its pathogenesis linked to toxic, polyglutamine (polyQ)-expanded mutant huntingtin fragments (mHTT). However, the mechanisms underlying the interaction between UBL3 and mHTT remain poorly understood.</p><p><strong>Methods: </strong>To elucidate this relationship, we performed hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) on postmortem brain tissue from HD patients. Gaussia princeps-based split-luciferase complementation assay and co-immunoprecipitation were employed to confirm the interaction between UBL3 and mHTT. Additionally, we conducted a HiBiT lytic detection assay to assess the influence of UBL3 on the intracellular sorting of mHTT. Finally, immunocytochemical staining was utilized to validate the colocalization and distribution of these proteins.</p><p><strong>Results: </strong>Our findings revealed UBL3-positive inclusions in the cytoplasm and nuclei of neurons throughout the striatum of HD patients. We discovered that UBL3 colocalizes and interacts with mHTT and modulates its intracellular sorting.</p><p><strong>Conclusions: </strong>These results suggest that UBL3 may play a significant role in the interaction and sorting of mHTT, contributing to the understanding of its potential implications in the pathophysiology of Huntington's disease.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1175-1188"},"PeriodicalIF":3.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504823","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}