N-acetylneuraminic acid (Neu5Ac) (Neu5Ac)

The intracellular sialic acid pool in skeletal muscle refers to the metabolic availability of N-acetylneuraminic acid (Neu5Ac), the predominant sialic acid in humans, which is essential for the post-translational modification of glycoproteins and glycolipids (Varki, 2008). In skeletal muscle, sialic acid is a critical component of the glycans on proteins such as alpha-dystroglycan, which maintains the structural integrity of the sarcolemma by linking the cytoskeleton to the extracellular matrix (Nishino et al., 2015). A depletion of this pool is the primary pathogenic mechanism in GNE myopathy (also known as Hereditary Inclusion Body Myopathy), a rare genetic disorder caused by mutations in the GNE gene that encodes the rate-limiting enzyme in the sialic acid biosynthetic pathway (Lochmüller et al., 2023). Therapeutic strategies focus on replenishing this pool through substrate replacement therapy, using exogenous sialic acid or its precursors like N-acetylmannosamine (ManNAc), to restore proper protein sialylation and prevent muscle degeneration (Jay et al., 2009). Maintaining an adequate intracellular sialic acid pool is vital for preventing the formation of rimmed vacuoles and slowing the progression of muscle weakness.

Other names

Sialic acidN-acetylneuraminateNANAIntracellular sialic acid pool

Substrate replacement therapy to bypass enzymatic blocks in the biosynthetic pathway and restore the intracellular sialic acid pool for glycoprotein sialylation.