This study investigates the role of Cathepsin D (CTSD), a lysosomal protease, in neurodegeneration and amyloid-beta (Aβ) accumulation. Researchers generated a mouse model with overexpression of human CTSD specifically in the nervous system to assess its effects on lifespan, proteasomal function, and Aβ42 accumulation in systemic CTSD Knockout mice.
Overexpression of CTSD in the nervous system extended the lifespan of systemic CTSD Knockout mice, partially rescued proteasomal deficits, and reduced the accumulation of Aβ42. These findings suggest that CTSD plays a crucial role in maintaining proteostasis and preventing neurodegeneration associated with lysosomal dysfunction.
The study utilized a transgenic mouse model where human CTSD cDNA was inserted into the Hprt locus with a floxed STOP cassette under the control of the ubiquitous CAG promoter. Crossing these mice with Nestin-Cre mice allowed for nervous system-specific overexpression of CTSD upon Cre-mediated recombination.
Neurodegeneration, Lysosomal storage disorders, Amyloid-beta, Proteostasis, Cathepsin D
Transgenic mouse model, Nervous system-specific overexpression, Cre-loxP system, Lysosomal protease, Neurodegenerative disease model
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
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