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Cell-autonomous and non-cell-autonomous toxicity in polyglutamine diseases
Fabio Sambataro1, Maria Pennuto
1Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova 16163, Italy.
Progress in Neurobiology
|November 9, 2011
Summary
Polyglutamine diseases involve neurodegeneration. New research shows these disorders are not just cell-autonomous, but also influenced by non-neuronal cells, impacting disease mechanisms.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Polyglutamine diseases are neurodegenerative disorders linked to expanded polyglutamine tracts in specific genes.
- Selective neuronal degeneration occurs despite widespread protein expression, suggesting cell-autonomous mechanisms.
- Previous understanding viewed these diseases as cell-autonomous, focusing on intrinsic neuronal damage.
Purpose of the Study:
- To describe cell-autonomous and non-cell-autonomous mechanisms in polyglutamine disease pathogenesis.
- To explore the role of non-neuronal cells in selective neuronal damage.
- To update the understanding of polyglutamine disease mechanisms.
Main Methods:
- Review of cell-autonomous and non-cell-autonomous mechanisms.
- Analysis of polyglutamine protein expression and toxicity.
- Examination of animal models with conditional polyglutamine protein expression.
Main Results:
- Polyglutamine diseases are not solely cell-autonomous.
- Toxicity in neighboring non-neuronal cells contributes significantly to neuronal damage.
- Mechanisms involve various cell types including neurons, skeletal muscle, glia, and germinal cells.
Conclusions:
- Polyglutamine disease pathogenesis involves both cell-autonomous and non-cell-autonomous pathways.
- Non-neuronal cell toxicity is a critical factor in selective neurodegeneration.
- A revised view of polyglutamine diseases incorporates broader cellular interactions.
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