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Author ORCID Identifier
https://orcid.org/0000-0001-9144-7315
AccessType
Campus-Only Access for One (1) Year
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Molecular and Cellular Biology
Year Degree Awarded
2021
Month Degree Awarded
May
First Advisor
Scott Garman
Subject Categories
Biochemistry | Molecular Biology | Structural Biology
Abstract
Human lysosomal neuraminidase 1 (hNEU1) is an exo-a-sialidase which cleaves a(2-3) and a(2-6) linked sialic acids on glycoproteins in the lysosome. Deficiency of hNEU1 in the lysosome results in sialidosis, a lysosomal storage disease. Currently there is no effective treatment for sialidosis, which leads to a rising interest in discovering potential therapies. Here we presented a small molecule, α-D-N-acetylneuraminic acid (NANA), increases the protein amount and activity of both wild-type hNEU1 and three different hNEU1 mutations found in sialidosis patients in our mammalian cell system, suggesting that NANA works as a potential pharmacological chaperone for hNEU1 and provides a good scaffold for the development of pharmacological chaperone therapy for sialidosis. We also compared NANA with two potential treatments for sialidosis using MG132, a small molecule proteostasis regulator, or lysosomal protective protein/cathepsin A (PPCA), an auxiliary protein for hNEU1, and demonstrated that using MG132 or PPCA with NANA as potential combined treatments for sialidosis can enhance the enzymatic activity of hNEU1 in mammalian cells.
DOI
https://doi.org/10.7275/22496871.0
Recommended Citation
Chu, Di, "PHARMACOLOGICAL CHAPERONING OF HUMAN LYSOSOMAL NEURAMINIDASE 1" (2021). Doctoral Dissertations. 2170.
https://doi.org/10.7275/22496871.0
https://scholarworks.umass.edu/dissertations_2/2170