This review summarizes evidence linking polysialic acid (polySia), its synthase ST8SIA2, and the sialidase-mediated degradation pathway to psychiatric and neurodegenerative disorders including Alzheimer’s and Parkinson’s disease, with emphasis on connections to neuroinflammation.

Highlights a biologically plausible but underexplored pathway (polySia/ST8SIA2/sialidase) that could yield biomarkers or enzyme-targeted strategies to modulate neuroinflammation in Parkinson’s, though it is a broad review with limited direct, actionable therapeutic data.

This chapter reviews the relationship between polysialic acid (polySia), its biosynthetic enzyme ST8SIA2, and brain diseases, particularly psychiatric disorders such as schizophrenia, bipolar, and autism spectrum disorders, as well as neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. We also focus on the connection between inflammation and the polySia degradation enzyme, sialidase (neuraminidase).