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Updated: Jun 26, 2026
Bioluminescence Imaging of Neuroinflammation in Transgenic Mice After Peripheral Inoculation of Alpha-Synuclein Fibrils
Published on: April 13, 2017
The neuronal expression of MYC causes a neurodegenerative phenotype in a novel transgenic mouse
Hyoung-gon Lee1, Gemma Casadesus, Akihiko Nunomura
1Department of Pathology, Case Western Reserve University, 2103 Cornell Rd., Cleveland, OH 44106, USA. hyoung-gon.lee@case.edu
Abstract:
Many different proteins associated with the cell cycle, including cyclins, cyclin-dependent kinases, and proto-oncogenes such as c-MYC (MYC), are increased in degenerating neurons. Consequently, an ectopic activation of the cell cycle machinery in neurons has emerged as a potential pathogenic mechanism of neuronal dysfunction and death in many neurodegenerative diseases, including Alzheimer's disease. However, the exact role of cell cycle re-entry during disease pathogenesis is unclear, primarily because of the lack of relevant research models to study the effects of cell cycle re-entry on mature neurons in vivo. To address this issue, we developed a new transgenic mouse model in which forebrain neurons (CaMKII-MYC) can be induced to enter the cell cycle using the physiologically relevant proto-oncogene MYC to drive cell cycle re-entry. We show that such cell cycle re-entry results in neuronal cell death, gliosis, and cognitive deficits. These findings provide compelling evidence that dysregulation of cell cycle re-entry results in neurodegeneration in vivo. Our current findings, coupled with those of previous reports, strengthen the hypothesis that neurodegeneration in Alzheimer's disease, similar to cellular proliferation in cancer, is a disease that results from inappropriate cell cycle control.
Insights
Dysregulated cell cycle re-entry in neurons causes neurodegeneration. This study developed a mouse model showing that activating the cell cycle in mature neurons leads to cell death and cognitive deficits, supporting a link to Alzheimer's disease.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Proteins regulating the cell cycle, like MYC, are elevated in degenerating neurons.
- Ectopic cell cycle activation in neurons is a suspected mechanism in neurodegenerative diseases, including Alzheimer's disease.
- The precise role of neuronal cell cycle re-entry in disease pathogenesis remains unclear due to a lack of suitable in vivo models.
Purpose of the Study:
- To investigate the in vivo effects of cell cycle re-entry in mature neurons.
- To establish a novel transgenic mouse model for studying neuronal cell cycle activation.
Main Methods:
- Development of a transgenic mouse model (CaMKII-MYC) enabling inducible cell cycle re-entry in forebrain neurons.
- Utilizing the proto-oncogene MYC to drive cell cycle re-entry in mature neurons.
Main Results:
- Induced cell cycle re-entry in forebrain neurons resulted in significant neuronal cell death.
- Observed gliosis and cognitive deficits in the CaMKII-MYC mice.
- Demonstrated that dysregulated cell cycle re-entry directly causes neurodegeneration in vivo.
Conclusions:
- Neuronal cell cycle re-entry is a pathogenic mechanism contributing to neurodegeneration.
- Findings support the hypothesis that neurodegenerative diseases like Alzheimer's disease involve aberrant cell cycle control, analogous to cancer.
- The CaMKII-MYC mouse model is a valuable tool for studying the role of cell cycle dysregulation in neurodegeneration.
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