Glycosylation in Neurodegeneration

Since our world is rapidly ageing, neurodegenerative diseases, affecting mostly the elderly population, represent one of the most common causes of death. They are associated with a wide range of rather unpleasant symptoms, such as memory loss, mood changes, tremors, hallucinations, psychosis, depression and many more. For many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis (ALS) and prion diseases, one or more proteins have been revealed as main culprits. However, the exact mechanisms of these diseases have not been confirmed yet, leading to difficulties in finding therapies.

Glycosylation is known to modify many proteins in our body (50‒60 %) and it is vital to take glycans into consideration whilst identifying the mechanisms. Glycans affect the structure and stability of proteins and have a role in modulating their function. Due to the fact that glycans are large, complex and heterogeneous structures, their characterization is quite challenging. Many improvements have been made in identifying disease-related proteins and monitoring the progression of diseases. However, glycans continue to be neglected, and it was not until recently that the interest in glycoproteomics has started to grow, showing their importance in providing treatment in different neurodegenerative diseases.

Alterations in protein glycosylation have been identified both in Alzheimer’s and Parkinson’s disease. One of the most important proteins involved in Alzheimer’s disease is the tau protein, where phosphorylation is the post-translational modification mostly investigated. However, more and more studies are showing the contribution of glycosylation in terms of stabilizing the protein against aggregation and slowing down the neurodegeneration. In Parkinson’s disease, aggregation of the protein called α-synuclein has been defined as the main event in the disease. However, recent studies have managed to link other potential glycoproteins from cerebrospinal fluid (CSF) and brain tissue to the disease pathogenesis. Another interesting study has shown differences in the immunoglobulin G (IgG) glycome between healthy individuals and patients with Parkinson’s disease, serving as a potential biomarker for the disease.

Although many more puzzles remain to be solved when it comes to the understanding of cellular processes in the brain, involving glycans in this story seems to be of great importance. It is known that changes in the glycan profile of human serum could serve as biomarkers for diseases such as cancer. Therefore, the potential of glycans as biomarkers for early detection of neurodegenerative diseases or finding therapeutic treatments remains to be further investigated.