NEU2

NEU1

NEU1 (Neuraminidase 1) is a gene that encodes an enzyme involved in the catabolism of sialic acids, which are important components of glycoproteins and glycolipids. This enzyme is crucial for the degradation of sialylated glycoconjugates in lysosomes. Mutations in the NEU1 gene can lead to a lysosomal storage disorder known as sialidosis.

Function

NEU1 encodes the enzyme neuraminidase 1, which is part of the lysosomal multienzyme complex. This complex also includes beta-galactosidase and cathepsin A. Neuraminidase 1 is responsible for the removal of sialic acid residues from glycoproteins and glycolipids, a critical step in the degradation and recycling of these molecules.

Clinical Significance

Mutations in the NEU1 gene are associated with sialidosis, a rare autosomal recessive lysosomal storage disorder. Sialidosis is characterized by the accumulation of sialylated oligosaccharides in tissues, leading to a range of symptoms including myoclonus, ataxia, and visual impairment. There are two main types of sialidosis:

• Type I Sialidosis: Also known as cherry-red spot myoclonus syndrome, this form presents in late childhood or adulthood with symptoms such as myoclonus, ataxia, and visual problems.
• Type II Sialidosis: A more severe form that presents in infancy or early childhood with additional symptoms such as developmental delay, hepatosplenomegaly, and dysostosis multiplex.

Genetic Information

The NEU1 gene is located on chromosome 6p21.3. It consists of several exons and encodes a protein that is approximately 415 amino acids in length. The gene is expressed in various tissues, with high expression in the placenta, kidney, and liver.

Pathophysiology

In normal physiology, neuraminidase 1 functions to cleave terminal sialic acid residues from glycoproteins and glycolipids, facilitating their breakdown and recycling. In sialidosis, mutations in NEU1 lead to deficient neuraminidase activity, resulting in the accumulation of sialylated substrates in lysosomes. This accumulation disrupts normal cellular function and leads to the clinical manifestations of the disease.

Diagnosis and Treatment

Diagnosis of sialidosis is based on clinical presentation, biochemical assays showing reduced neuraminidase activity, and genetic testing confirming mutations in the NEU1 gene. Currently, there is no cure for sialidosis, and treatment is primarily supportive and symptomatic. Research into enzyme replacement therapy and gene therapy is ongoing.

Research Directions

Current research on NEU1 focuses on understanding the molecular mechanisms underlying sialidosis and developing potential therapies. Studies are exploring the use of small molecules to enhance residual neuraminidase activity and the feasibility of gene therapy to correct the underlying genetic defect.

Also see

• Sialidosis
• Lysosomal storage disorder
• Glycoprotein
• Glycolipid