Modeling Huntington's Disease with Inducible Mutant Huntingtin in Neuronal Cells
Author Information
Author(s): Andreas Weiss, Ana Roscic, Paolo Paganetti
Primary Institution: Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland
Hypothesis
It is unclear how the pathogenic mechanisms initiated by mutant huntingtin relate to each other or if they can be reversed by pharmacological intervention.
Conclusion
The developed neuronal cell lines with inducible expression of wild type and mutant huntingtin represent a reliable in vitro system for modeling Huntington's disease.
Supporting Evidence
- Inducible expression of mutant huntingtin led to transcriptional dysregulation similar to that observed in Huntington's disease patients.
- Cell lines developed showed pathological hallmarks of Huntington's disease, including cell death and impaired mitochondrial function.
- Expression of wild-type huntingtin was found to have neuroprotective effects compared to mutant huntingtin.
Takeaway
Researchers created special brain cells that can turn on and off a gene related to Huntington's disease, helping them study how the disease works and test new treatments.
Methodology
The study involved creating neuronal cell lines with inducible expression of normal and mutant huntingtin fragments and analyzing their effects on cellular functions.
Potential Biases
Potential bias due to the use of a single cell line and the specific conditions under which experiments were conducted.
Limitations
The model may not fully capture all aspects of Huntington's disease pathology and relies on specific cell lines.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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