Cathepsin D's Role in Alpha-Synuclein Processing and Toxicity
Author Information
Author(s): Valerie Cullen, Maria Lindfors, Juliana Ng, Anders Paetau, Erika Swinton, Piotr Kolodziej, Heather Boston, Paul Saftig, John Woulfe, Mel B Feany, Liisa Myllykangas, Michael G Schlossmacher, Jaana Tyynelä
Primary Institution: Brigham & Women's Hospital, Harvard Medical School
Hypothesis
How does Cathepsin D expression affect alpha-synuclein processing and toxicity?
Conclusion
Cathepsin D can degrade excess alpha-synuclein, and its deficiency leads to increased toxicity and aggregation of alpha-synuclein.
Supporting Evidence
- Over-expression of Cathepsin D reduced alpha-synuclein levels in cell cultures.
- Cathepsin D deficiency in mice led to increased insoluble alpha-synuclein aggregates.
- Immunohistochemical studies showed altered alpha-synuclein distribution in Cathepsin D-deficient brains.
- Drosophila models demonstrated enhanced alpha-synuclein toxicity in the absence of Cathepsin D.
Takeaway
Cathepsin D helps break down a protein called alpha-synuclein, and when there's not enough of it, the protein can build up and cause problems in the brain.
Methodology
The study used cell cultures and mouse models to examine the effects of Cathepsin D on alpha-synuclein levels and toxicity.
Limitations
The study primarily focused on specific animal models and may not fully represent human conditions.
Participant Demographics
Mice and Drosophila models were used, including both wild-type and genetically modified strains.
Statistical Information
P-Value
p<0.01
Statistical Significance
p<0.01
Digital Object Identifier (DOI)
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