The Potential Role of Molecular Chaperones in Ngly1 Deficient Zebrafish

Zachary Jones ¹, Marie Mooney ¹, and Szymon Ciesielski ²

University of North Florida
1. Department of Biology
2. Department of Chemistry and Biochemistry

Congenital Disorders of Deglycosylation (CDDGs) are rare diseases characterized by mutations in the genes responsible for the removal of carbohydrate attachments on glycoproteins. The removal of these carbohydrate attachments is necessary for the proper degradation of misfolded glycoproteins. The specific gene of focus in this project is NGLY1, and the term “Ngly1 Deficiency” is used to describe the disease that results from biallelic loss of function mutations in the gene. Some common symptoms of NGLY1 Deficiency in humans include developmental delay, failure to thrive, and intellectual/physical disability. Ngly1 plays an important role in the degradation of glycoproteins by completely cleaving off the carbohydrate attachments. In the absence of Ngly1, carbohydrates aren’t properly cleaved off which results in the accumulation of misfolded glycoproteins. These misfolded glycoproteins are speculated to be the cause of the symptoms observed in patients with Ngly1 Deficiency. The way the cell typically handles misfolded proteins is with a special family of proteins called molecular chaperones. The function of molecular chaperones is to facilitate the refolding or degradation of misfolded proteins within the cell. In this project, we are exploring if molecular chaperones play a role in the removal of accumulated misfolded glycoproteins in Ngly1 deficiency within the species Danio rerio (Zebrafish).

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