Article
Biochemistry & Molecular Biology
Martina Sucha, Simona Benediktova, Filip Tichanek, Jan Jedlicka, Stepan Kapl, Dana Jelinkova, Zdenka Purkartova, Jan Tuma, Jitka Kuncova, Jan Cendelin
Summary: This study aimed to explore the potential of edaravone to slow down SCA1 progression in a mouse knock-in SCA1 model. However, the results showed that edaravone did not have any plausible therapeutic effect on either behavioral dysfunctions or other disease hallmarks in SCA1 mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Lucas Schenatto Sena, Renan Barbosa Lemes, Gabriel Vasata Furtado, Maria Luiza Saraiva-Pereira, Laura Bannach Jardim
Summary: This study adapted a mathematical model to describe the dynamics of CAG repeat expansions and estimate how many generations descendants of a de novo expansion can last. The model incorporates factors such as anticipation, fitness, and allelic segregation and is supported by empirical data.
FRONTIERS IN GENETICS
(2023)
Article
Clinical Neurology
Rebekah Koppenol, Andre Conceicao, Ines T. Afonso, Ricardo Afonso-Reis, Rafael G. Costa, Sandra Tome, Diogo Teixeira, Joana Pinto da Silva, Jose Miguel Codesso, David V. C. Brito, Liliana Mendonca, Adriana Marcelo, Luis Pereira de Almeida, Carlos A. Matos, Clevio Nobrega
Summary: Koppenol et al. demonstrate that overexpression of G3BP1 reduces aggregation of ataxin-2 and ataxin-3 in cell models of SCA2 and SCA3. Lentiviral delivery of G3BP1 leads to improved motor function and neuropathology in preclinical models, suggesting its potential as a therapeutic target for polyQ disorders.
Article
Biology
Pawel Joachimiak, Adam Ciesiolka, Emilia Kozlowska, Pawel M. Switonski, Grzegorz Figura, Agata Ciolak, Grazyna Adamek, Magdalena Surdyka, Zaneta Kalinowska-Poska, Maciej Figiel, Nicholas S. S. Caron, Michael R. R. Hayden, Agnieszka Fiszer
Summary: This study used SNP variants to quantitatively determine the allele-specific expression levels in patient-derived cell lines for spinocerebellar ataxia type 3 (SCA3) and Huntington's disease (HD). They found differences in allele expression levels and developed a reliable and quantitative method using SNP-based droplet digital PCR (ddPCR) to analyze low abundant transcripts. This allele-selective approach provides insights into allele-related mechanisms and can improve understanding of polyglutamine diseases.
Article
Clinical Neurology
Joshua J. White, Laurens W. J. Bosman, Francois G. C. Blot, Catarina Osorio, Bram W. Kuppens, Wilhelmina H. J. J. Krijnen, Charlotte Andriessen, Chris De Zeeuw, Dick Jaarsma, Martijn Schonewille
Summary: Purkinje cells in a mouse model expressing human ATXN1 with a polyQ expansion show relative sparing of certain subpopulations, maintaining normal physiological function. The absence of mutant ATXN1 protein expression in less affected Purkinje cells may explain their relative resistance to pathology. The study suggests that specific subpopulations of Purkinje cells can be spared in a model of widespread degeneration, preserving normal behaviors within the cerebellum's modular map.
Article
Cell Biology
Karen Jansen-West, Tiffany W. Todd, Lillian M. Daughrity, Mei Yue, Jimei Tong, Yari Carlomagno, Giulia Del Rosso, Aishe Kurti, Caroline Y. Jones, Judith A. Dunmore, Monica Castanedes-Casey, Dennis W. Dickson, Zbigniew K. Wszolek, John D. Fryer, Leonard Petrucelli, Mercedes Prudencio
Summary: Researchers developed a new mouse model of SCA3 that mimics several features of the human disease, including locomotor defects, cerebellar-specific neuronal loss, ATXN3 inclusions, and TDP-43 pathology. They also discovered that polyQ-ATXN3 protein levels in the plasma correlated with measures of cerebellar degeneration and locomotor deficits in SCA3 mice, indicating its potential as a biomarker for SCA3.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Victor Olmos, Neha Gogia, Kimberly Luttik, Fatema Haidery, Janghoo Lim
Summary: SCA1 is a late-onset, progressive, dominantly inherited genetic disease characterized by the loss of Purkinje cells in the cerebellum and motor deficits. In addition to these symptoms, there are also extra-cerebellar effects such as respiratory problems, cognitive defects, memory impairment, anxiety, and depression. The existing gap in research on extra-cerebellar regions in SCA1 highlights the need for further investigation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Cell Biology
Caila A. Pilo, Alexandra C. Newton
Summary: Protein kinase C gamma (PKCγ) isozyme plays a role in signal transduction within cells and its aberrant expression may be associated with certain cancers and neurodegenerative disorders such as SCA14. However, the exact mechanisms and roles of PKCγ in these diseases are still not fully understood.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Ana F. Ferreira, Mafalda Raposo, Emily D. Shaw, Naila S. Ashraf, Filipa Medeiros, Maria de Fatima Brilhante, Matthew Perkins, Joao Vasconcelos, Teresa Kay, Maria do Carmo Costa, Manuela Lima
Summary: Machado-Joseph disease (MJD) is a dominant neurodegenerative disease caused by an expanded CAG repeat in the ATXN3 gene. Dysregulation of mitochondrial apoptosis and altered expression of apoptosis genes/proteins are observed in MJD patients and mice. Tissue-specific vulnerability to apoptosis and partially replicated gene expression profiles in MJD mouse model were found, indicating complex mechanisms of MJD pathogenesis.
Article
Nutrition & Dietetics
Yu-Ling Wu, Jui-Chih Chang, Hai-Lun Sun, Wen-Ling Cheng, Yu-Pei Yen, Yong-Shiou Lin, Yi-Chun Chao, Ko-Hung Liu, Ching-Shan Huang, Kai-Li Liu, Chin-San Liu
Summary: This study demonstrated the protective effect of Coenzyme Q10 (CoQ10) in spinocerebellar ataxia type 3 (SCA3) treatment. Results showed that CoQ10 supplementation significantly improved locomotion in mice and restored the structure of the cerebellar layers. Moreover, CoQ10 facilitated the clearance of mutant ataxin-3 protein through autophagy and restored the expression of antioxidant enzymes. Additionally, CoQ10 treatment prevented muscle weight loss and muscle atrophy in diseased mice.
Article
Biochemistry & Molecular Biology
Ines T. Afonso, Patricia Lima, Andre Conceicao, Carlos A. Matos, Clevio Nobrega
Summary: Age plays an important role in the onset and progression of SCA2 disease. Aged animals injected with expanded ataxin-2 showed aggravated SCA2 disease phenotype, indicating the significance of aging in SCA2 pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Public, Environmental & Occupational Health
Robert K. Szymczak, Magdalena Sawicka, Jan Pyrzowski
Summary: Spinocerebellar ataxias are rare genetic diseases characterized by disturbances in gait, balance, and uncoordinated movements. In high-altitude environments, these symptoms may also resemble those of high-altitude cerebral edema.
JOURNAL OF TRAVEL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Roberta A. Gottlieb, Honit Piplani, Jon Sin, Savannah Sawaged, Syed M. Hamid, David J. Taylor, Juliana de Freitas Germano
Summary: Mitochondrial quality control relies on various mechanisms such as selective elimination of damaged mitochondria, mitochondrial biogenesis, fusion, and fission, which are crucial for maintaining heart health.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Mary Adebayo, Seema Singh, Ajay Pratap Singh, Santanu Dasgupta
Summary: Mitochondria are dynamic organelles inherited maternally, fulfilling cellular energy demand and playing roles in cell signaling, metabolism, and apoptosis. Maintenance of mitochondrial integrity and homeostasis through fusion and fission is crucial, and imbalance can lead to various diseases.
Review
Biochemistry & Molecular Biology
Jirapong Vongsfak, Wasana Pratchayasakul, Nattayaporn Apaijai, Tanat Vaniyapong, Nipon Chattipakorn, Siriporn C. Chattipakorn
Summary: Cerebral ischemia and reperfusion injury can lead to poor oxygen supply, brain infarction, and an imbalance in mitochondrial dynamics, which plays a crucial role in cell survival and infarct area size regulation. Understanding and regulating mitochondrial dynamics may help prevent or treat cerebral injury.
Article
Biochemistry & Molecular Biology
Huan Ou-Yang, Shiao-Hsuan Yang, Wei Chen, Shang-Hsun Yang, Abdulkadir Cidem, Li-Ying Sung, Chuan-Mu Chen
Summary: This study found that flexible cruciform DNA structures play an important role in the integration of exogenous DNA into the chromosomes of transgenic animals. These DNA structures act as legible templates, promoting the integration of DNA into linear DNA or double-strand break alleles. Experimental results using the CRISPR/Cas9 system in NIH3T3 cells showed that the knock-in rate was significantly higher when using a 5' homologous arm inverted repeat donor plasmid that matched with ROSA gRNA compared to a knock-in reporter donor plasmid.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Ying-Cheng Chen, Ying-Wei Lan, Shiaw-Min Huang, Chih-Ching Yen, Wei Chen, Wan-Ju Wu, Theresa Staniczek, Kowit-Yu Chong, Chuan-Mu Chen
Summary: The study demonstrates that hAFMSCs can inhibit the proliferation, tumor growth, and invasion of PDAC cells by altering cell cycle and signaling pathways.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Environmental Sciences
Shih-Wei Chen, Han-Jie Lin, Stella Chin-Shaw Tsai, Cheng-Li Lin, Chung Y. Hsu, Tsai-Ling Hsieh, Chuan-Mu Chen, Kuang-Hsi Chang
Summary: This study aims to investigate the association between air pollution and chronic rhinosinusitis (CRS). Using databases from Taiwan's National Health Insurance and Air Quality Monitoring, the study found that higher levels of air pollutants, such as PM2.5, NO2, and PM10, were significantly associated with increased CRS risk.
Article
Cell & Tissue Engineering
Li-Kuang Tsai, Huan Ou-Yang, Jie Xu, Chuan-Mu Chen, Wei-Fang Chang, Li-Ying Sung
Summary: Multiple rounds of somatic cell nuclear transfer (SCNT), or recloning, do not further elongate the telomeres of genes that participate in telomere elongation and maintenance processes. This finding suggests that a single round of SCNT is a viable means to reprogram cells and elongate telomere lengths.
STEM CELLS AND DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Yu-Hsien Liu, Yu-Hsuan Chen, Chi-Hua Ko, Chia-Wen Kuo, Chih-Ching Yen, Wei Chen, Kowit-Yu Chong, Chuan-Mu Chen
Summary: ESRD patients experience increased cardiovascular events and hospitalizations due to oxidative stress and inflammation. This study identifies SOD3 and IL-18 as strong predictors for the first kidney disease-related hospitalization or death in ESRD patients.
Article
Biochemistry & Molecular Biology
Tsung-Teng Huang, Chuan-Mu Chen, Ying-Wei Lan, Song-Shu Lin, Kong-Bung Choo, Kowit-Yu Chong
Summary: This study demonstrates the anti-tumor activity of E7050 in multidrug-resistant uterine sarcoma cells, which is achieved by inducing apoptosis and cell cycle arrest. Mechanistically, E7050 exerts its effects by inhibiting the phosphorylation of multiple signaling pathways. In vivo experiments show that E7050 can significantly suppress tumor growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Han -In Yang, Pin -Yu Huang, Siew Chin Chan, Chih-Wei Tung, Pei-Hsun Cheng, Chuan-Mu Chen, Shang-Hsun Yang
Summary: The study found that miR-196a enhances the polymerization of neuronal microfilaments by suppressing IMP3 and upregulating IGF2, thereby promoting neurite outgrowth in Huntington's disease.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Review
Biochemistry & Molecular Biology
Hueng-Chuen Fan, Kuo-Liang Chiang, Kuang-Hsi Chang, Chuan-Mu Chen, Jeng-Dau Tsai
Summary: Comorbidities are common in children with epilepsy, and ADHD is one of the most prevalent comorbidities. The burden of ADHD in children with epilepsy is high and can negatively impact their clinical outcomes, psychosocial aspects, and quality of life. Stimulants have shown effectiveness and safety in treating comorbid ADHD, but further research is needed to establish their safety in randomized, double-blinded, placebo-controlled trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Tsung-Teng Huang, Chuan-Mu Chen, Song-Shu Lin, Ying-Wei Lan, Hsu-Chen Cheng, Kong-Bung Choo, Ching-Chiung Wang, Tse-Hung Huang, Kowit-Yu Chong
Summary: In this study, the anti-angiogenic activity of E7050 was evaluated in vitro and in vivo, and its mechanism of action was elucidated. E7050 was found to significantly inhibit the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs), as well as the neovessel formation in chick embryos. The underlying molecular mechanism involved the suppression of VEGFR2 phosphorylation and its downstream signaling pathway components. Moreover, E7050 showed efficacy in attenuating tumor growth and inhibiting angiogenesis in a xenograft model of multidrug-resistant uterine sarcoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Siew Chin Chan, Chih-Wei Tung, Chia-Wei Lin, Yun-Shiuan Tung, Po-Min Wu, Pei-Hsun Cheng, Chuan-Mu Chen, Shang-Hsun Yang
Summary: This study reveals the multifaceted role of miR-196a in Huntington's disease, including reducing reactive oxygen species levels and cell death through antioxidative effects, enhancing the transcription of antioxidant genes via the nuclear factor erythroid 2 pathway, and counteracting mutant Huntingtin protein aggregation through targeting ubiquitin-specific peptidase 15. These findings highlight the potential of miR-196a as a therapeutic avenue for ameliorating oxidative stress and neurodegeneration in Huntington's disease.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Yung-Tsung Kao, Chih-Ching Yen, Hueng-Chuen Fan, Jen-Kun Chen, Ming-Shan Chen, Ying-Wei Lan, Shang-Hsun Yang, Chuan-Mu Chen
Summary: This study investigated the use of human amniotic fluid mesenchymal stromal cells (hAFMSCs) through in utero transplantation (IUT) as a potential treatment for hemophilia A. The results showed that the transplanted human cells fused with the recipient liver and produced human FVIII protein. This approach significantly improved the coagulation issues in FVIII knockout mice with hemophilia A.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chi-Chien Lin, Kai-Cheng Chuang, Shih-Wei Chen, Ya-Hsuan Chao, Chih-Ching Yen, Shang-Hsun Yang, Wei Chen, Kuang-Hsi Chang, Yu-Kang Chang, Chuan-Mu Chen
Summary: Lactoferrin exhibits anti-inflammation and immunoregulation activities in OVA-induced allergic asthma, ameliorating lung injury, decreasing Th2 cytokines and allergen-specific antibodies production, and influencing the functions of dendritic cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)