The sulfation pattern of glycosaminoglycans in human brain development and neurological disorders such as Alzheimer's disease.

Abstract

Glycosaminoglycans (GAGs) are modified by various sulfotransferases and endosulfatases. The resulting sulfation patterns are formed, influencing numerous functions. Sulfation leads to a strong negative charge on GAGs, inducing specific interactions with proteins such as signaling ligands and pathogenicity factors, impacting cellular functions and disease onset. Although a long history of research has greatly advanced our understanding of GAGs and the sulfation patterns in model organisms, studies of human brain development and the pathogenesis of neurological diseases are in their infancy. To elucidate the role of the sulfation patterns in the human brain, it is necessary to determine the interplay of factors such as core proteins, GAG elongation enzymes, and sulfotransferases in a hierarchical manner. In recent years, technological advances in, for example, genomic mutation analysis, single-cell analysis, and in vitro brain development models, have begun to inform our understanding of the role of the sulfation patterns in human brain development and neurological disorders such as Alzheimer's disease.