DISEASE MODELS INVOLVING GENE MUTATION AND KNOCKOUT IN THE N-LINKED GLYCAN BIOSYNTHESIS PATHWAY

The N-linked glycan biosynthesis pathway is a complex process that plays a crucial role in the synthesis of proteins in eukaryotic cells. Any disruptions or mutations in this pathway can lead to a wide range of diseases, including cancer, neurodegenerative disorders, and metabolic disorders. In this section, we will discuss some of the disease models involving gene mutation and knockout in the N-linked glycan biosynthesis pathway.

1) Cancer:

Glycans play a critical role in cancer development and progression. Mutations in the N-linked glycan biosynthesis pathway can lead to the production of aberrant glycans that can promote cancer cell growth, survival, and metastasis. For example, mutations in the gene encoding the enzyme O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) have been associated with an increased risk of colorectal cancer. OGT is responsible for adding a glucosamine molecule to proteins, which is important for their proper folding and function. In cancer cells, the loss of OGT function can lead to the production of aberrant glycans that promote cell growth and survival.

2) Neurodegenerative disorders:

Mutations in the N-linked glycan biosynthesis pathway have also been implicated in neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. For example, mutations in the gene encoding the enzyme mannosidase-alpha (MAN2A1) have been associated with an increased risk of Alzheimer’s disease. MAN2A1 is responsible for removing mannose residues from glycoproteins, which is important for their proper folding and function. In Alzheimer’s disease, the loss of MAN2A1 function can lead to the accumulation of aberrant glycans that promote the formation of amyloid plaques and neurodegeneration.

3) Metabolic disorders:

Mutations in the N-linked glycan biosynthesis pathway can also lead to metabolic disorders such as type 2 diabetes and obesity. For example, mutations in the gene encoding the enzyme fucosyltransferase 2 (FUT2) have been associated with an increased risk of type 2 diabetes. FUT2 is responsible for adding fucose residues to glycoproteins, which is important for their proper folding and function. In type 2 diabetes, the loss of FUT2 function can lead to the accumulation of aberrant glycans that promote insulin resistance and glucose intolerance.

In conclusion, the N-linked glycan biosynthesis pathway plays a critical role in the synthesis of proteins in eukaryotic cells, and any disruptions or mutations in this pathway can lead to a wide range of diseases, including cancer, neurodegenerative disorders, and metabolic disorders. Understanding the role of glycans in these diseases is crucial for the development of effective treatments and therapies.