Glycoprotein Hydrogen-Bonding Hypothesis and Its Relationship with Other Mechanisms of Molecular Memory

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The glycoprotein hydrogen-bonding hypothesis proposes that long-term memory persistence may involve activity-dependent conformational states in synaptic glycoproteins, stabilised by cooperative hydrogen-bond networks among protein backbones, glycans and structured water. This review evaluates the hypothesis against current knowledge of synaptic plasticity, glycoproteomics, engram biology and protein dynamics. Glycoproteins have properties that make them plausible contributors to synaptic stabilisation: structural diversity, glycosylation-dependent folding, dense hydration shells, and the capacity to participate in extracellular and membrane-associated molecular assemblies. There is growing evidence that glycoproteins play a central role in synaptic plasticity. Transient quantum effects such as proton or electron tunnelling may, in principle, influence local molecular transitions. Glycoprotein conformational states may help stabilise synaptic changes within engram-related circuits.