Abstract
Neurodegenerative diseases (NDs) affect millions of people worldwide. Characterized by the functional loss and death of neurons, NDs lead to symptoms (dementia and seizures) that affect the daily lives of patients. In spite of extensive research into NDs, the number of approved drugs for their treatment remains limited. There is therefore an urgent need to develop new approaches for the prevention and treatment of NDs. Glycans (carbohydrate chains) are ubiquitous, abundant, and structural complex natural biopolymers. Glycans often covalently attach to proteins and lipids to regulate cellular recognition, adhesion, and signaling. The importance of glycans in both the developing and mature nervous system is well characterized. Moreover, glycan dysregulation has been observed in NDs such as Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Therefore, glycans are promising but underexploited therapeutic targets. In this review, we summarize the current understanding of glycans in NDs. We also discuss a number of natural products that functionally mimic glycans to protect neurons, which therefore represent promising new therapeutic approaches for patients with NDs.
Highlights
Glycans are ubiquitous across the natural world and can be found in both prokaryotes and eukaryotes
advanced glycation end-products (AGEs) upregulate the expression of BACE1 and Sirt1 expression via reactive oxygen species (ROS) [94], and clinical experiments indicated high levels of AGEs could influence the functional mobility in the aged population [95]
Changes in glycans have been observed in Huntington’s disease (HD) transgenic animals: increased core-fucosylated N-glycans were detected in the brain; increased sialylated biantennary type glycans and bisecting GlcNAc type glycans were detected in the serum; and decreased core 1-type O-glycans were detected in the serum, while core 2 type
Summary
Glycans are ubiquitous across the natural world and can be found in both prokaryotes and eukaryotes. Glycans are carbohydrate chains (monosaccharides, oligosaccharides, or polysaccharides) that either exist in a free state or attached to proteins and lipids [1]. The base glycan structure comprises monomeric residues (monosaccharides) containing five or six carbon rings, other more complicated monosaccharides exist [4]. The monosaccharide residues link to each other through covalent glycosidic bonds in multiple configurations to form oligosaccharides and polysaccharides. The hydroxyl group of one monosaccharide residue can potentially bind to any anomeric carbon of another monosaccharide residue to form glycosidic bonds [4]. Various glycosidic bond configurations based on the stereochemistry of the anomeric carbon result in diverse biological functions [5]. Certain complex monosaccharides are themselves essential for specific biological functions.
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