Interferon-Beta Gene Therapy Reverses Parkinson's Disease Symptoms in Mouse Model
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By LabMedica International staff writers Posted on 19 Oct 2015 |
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Image: Micrograph showing brain cells with signs of Parkinson\'s disease (Photo courtesy of the University of Copenhagen).
The lack of cytokine interferon-beta (IFN-beta) signaling in a mouse model caused formation of Lewy bodies in the animals' brains and triggered neurodegeneration similar to that seen in the brains of human Parkinson's disease (PD) patients.
A Lewy body is composed of the protein alpha-synuclein associated with other proteins, such as ubiquitin, neurofilament protein, and alpha B crystalline. Lewy bodies are a feature of alpha-synucleinopathies such as dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. They are also found in the CA2-3 region of the hippocampus in Alzheimer's disease.
Investigators at the University of Copenhagen (Denmark) reported in the October 8, 2015, issue of the journal Cell that lack of cytokine interferon-beta (IFN-beta) signaling caused spontaneous neurodegeneration in the absence of neurodegenerative disease-causing mutant proteins. Mice lacking IFN-beta function exhibited motor and cognitive learning impairments with accompanying alpha-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-beta signaling caused defects in neuronal autophagy prior to alpha-synucleinopathy, which was associated with accumulation of aged and dysfunctional mitochondria.
Recombinant IFN-beta treatment of mice lacking the cytokine reversed PD symptoms by promoting neurite growth and branching, autophagy flux, and alpha-synuclein degradation in neurons. In addition, lentiviral transfection of the interferon-beta gene and subsequent IFN-beta overexpression prevented dopaminergic neuron loss in a familial Parkinson’s disease model.
"This is one of the first genes found to cause pathology and clinical features of non-familial PD and DLB (dementia with Lewy bodies), through accumulation of disease-causing proteins. It is independent of gene mutations known from familial PD and when we introduced IFN-beta-gene therapy, we could prevent neuronal death and disease development. Our hope is that this knowledge will enable development of more effective treatment of PD," said senior author Dr. Shohreh Issazadeh-Navikas, head of the neuroinflammation unit at the University of Copenhagen.
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University of Copenhagen
A Lewy body is composed of the protein alpha-synuclein associated with other proteins, such as ubiquitin, neurofilament protein, and alpha B crystalline. Lewy bodies are a feature of alpha-synucleinopathies such as dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. They are also found in the CA2-3 region of the hippocampus in Alzheimer's disease.
Investigators at the University of Copenhagen (Denmark) reported in the October 8, 2015, issue of the journal Cell that lack of cytokine interferon-beta (IFN-beta) signaling caused spontaneous neurodegeneration in the absence of neurodegenerative disease-causing mutant proteins. Mice lacking IFN-beta function exhibited motor and cognitive learning impairments with accompanying alpha-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-beta signaling caused defects in neuronal autophagy prior to alpha-synucleinopathy, which was associated with accumulation of aged and dysfunctional mitochondria.
Recombinant IFN-beta treatment of mice lacking the cytokine reversed PD symptoms by promoting neurite growth and branching, autophagy flux, and alpha-synuclein degradation in neurons. In addition, lentiviral transfection of the interferon-beta gene and subsequent IFN-beta overexpression prevented dopaminergic neuron loss in a familial Parkinson’s disease model.
"This is one of the first genes found to cause pathology and clinical features of non-familial PD and DLB (dementia with Lewy bodies), through accumulation of disease-causing proteins. It is independent of gene mutations known from familial PD and when we introduced IFN-beta-gene therapy, we could prevent neuronal death and disease development. Our hope is that this knowledge will enable development of more effective treatment of PD," said senior author Dr. Shohreh Issazadeh-Navikas, head of the neuroinflammation unit at the University of Copenhagen.
Related Links:
University of Copenhagen
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