Table 1.
Glycosylation in neurodegenerative diseases.
| Diseases | Protein/Gene Products | Known Glycosylation Types | Glycosylation Sites (confirmed) | Functions/Comments | |
|---|---|---|---|---|---|
| Alzheimer’s disease (AD) | APP | N-glycosylated | Asn467 | Asn496 | 1. Defects in N-glycosylation prevent the transportation and secretion of APP 2. O-glycosylated APP decreases Aβ secretion 3. Increase in tyrosine-linked glycan on Aβ fragments has been identified in the CSF samples of AD patients |
| O-GlcNAcylated (APP695) | Thr291 | Thr292 | |||
| Thr576 | |||||
| O-GlcNAcylated (APP770) | Ser597 | Ser606 | |||
| Ser611 | Thr616 | ||||
| Thr634 | Thr635 | ||||
| Ser662 | Ser680 | ||||
| BACE-1 | N-glycosylated | Asn153 | Asn172 | 1. Bisecting GlcNAc modification of BACE-1 increases Aβ production | |
| Asn223 | Asn354 | ||||
| Tau | N-glycosylated | Asn167 | Asn359 | 1. N-glycosylation of Tau appeared to be responsible for the maintenance of the PHFs structure 2. Level of O-GlcNAcylation of Tau is decreased in AD brains |
|
| Asn359 | |||||
| O-GlcNAcylated | Ser400 | Thr123 | |||
| Nicastrin | N-glycosylated | 16 potential sites | 1. Defects of O-GlcNAcylation decrease Aβ plaques 2. Function of N-glycosylated remains poorly understood |
||
| O-GlcNAcylated | Ser708 | ||||
| PS | None | ||||
| Parkinson’s disease (PD) | α-synuclein | O-GlcNAcylated | Thr33 | Thr44 | 1. Accumulation of O-linked glycosylation of α-synuclein was found in PD patients |
| Thr54 | Thr59 | ||||
| Thr64 | Thr72 | ||||
| Thr75 | Thr81 | ||||
| Thr87 | |||||
| Huntington’s disease (HD) | huntingtin | O-GlcNAcylated | N/A | 1. O-GlcNAcylation regulates clearance of mHtt 2. O-GlcNAcylation stimulates autophagy and reduces huntingtin aggregation |
|
| Multiple Sclerosis (MS) | TNF-α | N/A | N/A | 1. Absence of GlcNAc brancing in neurons induces apoptosis and promotes demyelination 2. N-glycan branching is required to prevent T cell hyperactivity, cytotoxic T lymphocyte antigen 4 (CTLA-4) endocytosis, spontaneous inflammatory demyelination in MS pathology |
|
| Amyotrophic Lateral Sclerosis (ALS) | SOD1 | N/A | N/A | 1. CSF IgG N-glycosylation as a potential biomarker for ALS 2. Altered expression of glycoproteins in the sera or CSF were detected in ALS patients |
|
AD, Alzheimer’s disease; APP, amyloid precursor protein; Aβ, amyloid beta; CSF, cerebrospinal fluid; GlcNAc, N-acetylglucosamine; BACE-1, β-site APP-cleaving enzyme 1; PHFs, paired helical filaments; PS, presenilin; PD, Parkinson’s disease; HD, Huntington’s disease; mHtt, mutant huntingtin; MS, multiple sclerosis; TNF-α, tumor necrosis factor alpha; ALS, amyotrophic lateral sclerosis; SOD1, superoxide dismutase 1; Asn, asparagine; Thr, threonine; Ser, serine.