A5041724298- RNA regulation and disease
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Alzheimer's disease research and treatments
- interferon and immune responses
- Medicinal Plants and Neuroprotection
- Vascular Tumors and Angiosarcomas
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Treatment and Pharmacology
- Cancer Cells and Metastasis
- Cancer-related molecular mechanisms research
- Immune Response and Inflammation
- Tryptophan and brain disorders
National Tsing Hua University
2017-2025
Institute of Molecular Medicine
2017-2025
Gfap -antisense prevents disease with early treatment and reverses clinical phenotypes late in a rat model of Alexander disease.
Glial fibrillary acidic protein (GFAP) is classified as a type III intermediate filament predominantly expressed in mature astrocytes. It has the ability to self-assemble into 10 nm filaments vitro, making it particularly valuable for elucidating sequences essential assembly. In this study, we created series of deletion mutants targeting N-terminal, C-terminal, and central rod domains explore critical assembly GFAP filaments. The impact these deletions on formation was evaluated through...
Alexander disease (AxD) is a rare neurological disorder caused by dominant gain-of-function mutations in the gene for glial acidic fibrillary protein ( GFAP ). Expression of mutant results astrocyte dysfunction that ultimately leads to developmental delay, failure thrive, and intellectual motor impairment. The typically fatal, at present there are no preventative or effective treatments. To gain better understanding link between behavioral deficits AxD we recently developed rat model...
Neuroinflammation plays a central role in the pathophysiology of Alzheimer’s disease (AD). Compounds that suppress neuroinflammation have been identified as potential therapeutic targets for AD. Rhinacanthin C (RC), naphthoquinone ester found Rhinacanthus nasutus Kurz (Acanthaceae), is currently proposed an effective molecule against inflammation. However, exact RC on remains to be elucidated. In present study, we investigated effect modulating lipopolysaccharides (LPS), amyloid‐ β peptide...
Alexander disease is a primary genetic disorder of astrocytes caused by dominant mutations in the gene encoding glial fibrillary acidic protein (GFAP). How single-amino-acid changes can lead to cytoskeletal catastrophe and brain degeneration remains poorly understood. In this study, we have analyzed 14 missense located GFAP rod domain investigate how these affect vitro filament assembly. Whereas internal mutants assembled into filaments that were shorter than those wild type, end formed...
Alexander disease (AxD) caused by mutations in the coding region of GFAP is a neurodegenerative characterized astrocyte dysfunction, aggregation, and Rosenthal fiber accumulation. Although how cause not fully understood, fibers could be induced forced overexpression human this lethal mice implicate that an increase levels central to AxD pathogenesis. Our recent studies demonstrated intronic altering splicing, suggesting isoform expression lead protein aggregation dysfunction typify AxD. Here...
Alexander disease (AxD) is a neurodegenerative caused by heterozygous mutations in the GFAP gene, which encodes major intermediate filament protein of astrocytes. This characterized accumulation cytoplasmic aggregates, known as Rosenthal fibers. Antibodies specific to could provide invaluable tools facilitate studies normal biology and elucidate pathologic role this IF disease. While large number antibodies are available, few if any them have defined epitopes. Here we described...
Cisplatin chemotherapy causes myelosuppression and often limits treatment duration dose escalation in patients. Novel approaches to circumvent or lessen myelotoxicity may improve clinical outcome quality of life these Chlorella sorokiniana (CS) is a freshwater unicellular green alga exhibits encouraging efficacy immunomodulation anticancer preclinical studies. However, the CS on chemoprotection remains unclear. We report here, for first time, that extract (CSE) could protect normal myeloid...
Background: Alzheimer’s disease (AD) is a multifactorial disorder characterized by cognitive decline. Current available therapeutics for AD have limited clinical benefit. Therefore, preventive therapies interrupting the development of are critically needed. Molecules targeting multifunction to interact with various pathlogical components been considered improve therapeutic efficiency AD. In particular, herbal medicines multiplicity actions produce benefits on Bugu-M multi-herbal extract...
Abstract Background Alexander disease (AxD) is an autosomal‐dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acidic protein ( GFAP ) gene. Objectives The objective of this report to characterize clinical phenotype and identify genetic mutation associated with adult‐onset AxD. Methods A man presented progressive unsteadiness since age 16. Magnetic resonance imaging findings revealed characteristic features gene was screened, a candidate variant functionally...
Abstract Alexander disease (AxD) is a devastating leukodystrophy caused by gain of function mutations in GFAP , and the only available treatments are supportive. Recent advances antisense oligonucleotide (ASO) therapy have demonstrated that transcript targeting can be successful strategy for human neurodegenerative diseases amenable to this approach. We previously used mouse models AxD show Gfap -targeted ASO suppresses protein accumulation reverses pathology; however, mice mild phenotype...