Glycan Mimetics from Natural Products: New Therapeutic Opportunities for Neurodegenerative Disease

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.

Glycoproteins as diagnostic and prognostic biomarkers for neurodegenerative diseases: A glycoproteomic approach

“…Glycans can play important roles in cell functions by storing the biological information of glycoproteins. However, due to the analytical complexity, the progress of glycomics has lagged far behind genomics and proteomics (Wang et al., 2019).…”

Implications of Glycosylation in Alzheimer’s Disease

“…AD patients present with an abnormal glycan profile, and several studies have shown altered glycosylation patterns in these patients. Increased levels of bisecting GlcNAc, which is a special N -glycan structure highly expressed in the brain, have been revealed in AD patients ( Wang et al, 2019 ), together with an increased expression of the responsible converting enzyme GnT-III ( Akasaka-Manya et al, 2010 ). Studies in neuroblastoma cells have shown an upregulation of GnT-III in response to Aβ treatment, and reduced Aβ load in GnT-III transfected cells, hypothesizing a protective effect of N -glycans, and upregulation of GnT-III as an adaptive response in AD brains ( Akasaka-Manya et al, 2010 ).…”

“…As previously described, glycosylation is mainly regulated by the action of glycosidases and glycotransferases. Modulating the function of these enzymes could thus be a potential therapeutic strategy ( Wang et al, 2019 ). Furthermore, the increase in level of bisecting GlcNAc and decreased ST activity, together with the abnormal glycosylation linked to neuroinflammation presents potential new targets in AD treatment ( Table 4 ).…”

Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management

“…Among HS modifying enzymes, HPSE is definitely one of the most investigated as a cancer drug target [ 105 , 175 , 185 , 188 , 203 , 204 ]. Early observations of the powerful HPSE inhibitory activity of heparin lead the way for the screening of heparin/HS mimetics as HPSE inhibitors [ 102 , 205 , 206 , 207 , 208 ].…”