Distribution of Sialidase Activity and the Role of Sialidase in the Brain

Abstract

Sialic acid is an acidic monosaccaride and plays crucial roles in various membrane functions in mammalian central nervous systems. Sialidase removes sialic acid from sialoglycoconjugates and also plays crucial roles in many neural functions, including differentiation and maturation of neurons and learning and memory. Recently, we visualized extracellular sialidase activity on the membrane surface in the rat brain by using a highly sensitive fluorescent histochemical method. Myelin-abundant regions showed intense fluorescence in the rat brain. Although the hippocampus showed weak fluorescence in the brain, mossy fiber terminals in the hippocampus showed relatively intense fluorescence. In this review, we describe the distribution of sialidase activity in the brain and discuss the role of sialidase in myelin and the hippocampus. A. Introduction S i a l i d a s e r e m o v e s s i a l i c a c i d r e s i d u e s f r o m sialoglycoconjugates, such as glycoproteins and glycolipids.Four types of mammalian sialidase (Neu1, Neu2, Neu3 and Neu4) have been identified in mammalian tissues by their localization and enzymatic properties. These four types of sialidase were reported to be expressed in mammalian brains (1). Since sialidase extracellularly applied to the rat hippocampus influences many neural functions including memory, synaptic plasticity, axon outgrowth and neural differentiation, activities of endogenous sialidases on the extracellular membrane surface would also affect neural functions (2-5). Neu1, Neu2 and Neu3 show enzyme activity on the extracellular membrane surface. Neu1 specifically acts on low-molecular-weight substrates, including 4MU-Neu5Ac, oligosaccharides and glycopeptides (6,7). Neu1 is mainly located at lysosomes. Neu1 is relocalized from the lysosome to the cell surface with activation of T cells and differentiation of monocytes (8,9). Neu2 hydrolyzes gangliosides and glycoproteins at neutral pH. Neu2 is located mainly in the cytoplasm but also in plasma membranes in the mouse

Rapid regulation of sialidase activity in response to neural activity and sialic acid removal during memory processing in rat hippocampus

“…Neu4 catalyzes degradation of PSA as well as removal of sialic acid from glycoproteins, gangliosides, and oligosaccharides (26,27,30). PSA plays an important role in hippocampal synaptic plasticity and memory (2,3,6). In hippocampal MFs, the expression level of PSA on NCAM is related to synaptic maturation.…”

Preferential Accumulation of 14C-N-Glycolylneuraminic Acid over 14C-N-Acetylneuraminic Acid in the Rat Brain after Tail Vein Injection

“…In the hippocampus, it has been reported that sialyl signalling via gangliosides such as GQ1b and PSA, which bind to neural cell adhesion molecule (NCAM), is necessary for synaptic plasticity and memory [ 33 , 34 , 35 ]. Sialidase also plays important roles in many neural functions, including neural excitation, axonal elongation, differentiation and maturation [ 5 , 36 ]. Four types of mammalian sialidase (Neu1, Neu2, Neu3 and Neu4) have been identified in mammalian tissues by their localization and enzymatic properties.…”

“…The two most prevalent species of sialic acids existing in nature are N -acetylneuraminic acid (Neu5Ac) and N -glycolylneuraminic acid (Neu5Gc) [ 1 , 2 , 3 ]. Neu5Ac is abundantly contained in the mammalian brain and plays crucial roles in many neural functions such as memory, synaptic plasticity, brain development and neurological disorder [ 4 , 5 , 6 ]. In contrast, Neu5Gc is synthesized via the effect of cytidine monophospho- N -acetylneuraminic acid hydroxylase (CMAH), which catalyzes the conversion of cytidine 5'-monophosphate Neu5Ac (CMP-Neu5Ac) to CMP-Neu5Gc [ 7 ].…”

Visualization of Sialidase Activity in Mammalian Tissues and Cancer Detection with a Novel Fluorescent Sialidase Substrate

“…We developed novel fluorescent sialidase substrates for histochemical staining of sialidase activities in mammalian tissues. Since sialidase plays crucial roles in many biological functions including lysosomal catabolism, immune system and neural functions [2] , [31] , BTP-Neu5Ac is a powerful tool for detailed investigation of sialidase functions. Since the cytotoxicities of BTP-Neu5Ac and BTP were undetectable, BTP-Neu5Ac can be used for biological assay of sialidase in the living tissue, e.g.…”