Sialic Acid in Neurodegenerative and Psychiatric Disorders: From Molecular Regulation to Targeted Nanocarrier-Based Therapy.

In recent years, the exploration of molecular and cellular mechanisms underlying central nervous system (CNS) disorders has expanded beyond classical neurotransmitter- and receptor-based approaches toward a more integrated view including immune, metabolic, and glycosylation processes. Among these, sialic acid and its derivatives have emerged as critical regulators of neuronal communication, immune modulation, and synaptic plasticity. Their involvement ranges from maintaining neurochemical homeostasis under physiological conditions to contributing to the onset and progression of neurodegenerative and psychiatric diseases. Given the central role of sialylation in cellular recognition, receptor signaling, and blood-brain barrier (BBB) interactions, understanding these pathways provides valuable insight for the development of advanced therapeutic and diagnostic strategies. This review highlights recent evidence linking altered sialic acid metabolism and polysialylation to Alzheimer's disease and other neurodegenerative and psychiatric disorders. It further discusses the potential of sialic acid-related mechanisms as novel molecular targets and their integration into innovative nanocarrier-based drug delivery systems designed to improve brain penetration, selectivity, and therapeutic efficacy. Finally, current challenges and future perspectives in translating sialic acid-based approaches into clinical applications are addressed.