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Cathepsin K is a potent disaggregase of α-synuclein fibrils.

Biochemical and biophysical research communications (2020-08-21)
Ryan P McGlinchey, Shannon M Lacy, Robert L Walker, Jennifer C Lee
RÉSUMÉ

The intracellular accumulation of α-synuclein (α-syn) amyloid fibrils is a hallmark of Parkinson's disease. Because lysosomes are responsible for degrading aggregated species, enhancing lysosomal function could alleviate the overburden of α-syn. Previously, we showed that cysteine cathepsins (Cts) is the main class of lysosomal proteases that degrade α-syn, and in particular, CtsL was found to be capable of digesting α-syn fibrils. Here, we report that CtsK is a more potent protease for degrading α-syn amyloids. Using peptide mapping by liquid chromatography with mass spectrometry, critical cleavage sites involved in destabilizing fibril structure are identified. CtsK is only able to devour the internal regions after the removal of both N- and C-termini, indicating their protective role of the amyloid core from proteolytic attack. Our results suggest that if overexpressed in lysosomes, CtsK has the potential to ameliorate α-syn pathology.

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Description du produit

Sigma-Aldrich
Leupeptine, microbial, ≥90% (HPLC)
Sigma-Aldrich
Cathepsin B from human liver, buffered aqueous solution, ≥1,500 units/mg protein (E1%/280)
Sigma-Aldrich
Cathepsin L from human liver, ≥0.5 units/mg protein, solution
Sigma-Aldrich
Cathepsin D from human liver, lyophilized powder, ≥250 units/mg protein (E1%/280)
Sigma-Aldrich
Cathepsin F Active human, recombinant, expressed in FreeStyle 293-F cells, ≥90% (SDS-PAGE)
Sigma-Aldrich
Cathepsin V Active human, recombinant, expressed in FreeStyle 293-F cells, ≥90% (SDS-PAGE)