New insight into protein glycosylation in the development of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disease that seriously endangers the physical and mental health of patients, however, there are still no effective drugs or methods to cure this disease up to now. Protein glycosylation is the most common modifications of the translated proteins in eukaryotic cells. Recently many researches disclosed that aberrant glycosylation happens in some important AD-related proteins, such as APP, Tau, Reelin and CRMP-2, etc, suggesting a close link between abnormal protein glycosylation and AD. Because of its complexity and diversity, glycosylation is thus considered a completely new entry point for understanding the precise cause of AD. This review comprehensively summarized the currently discovered changes in protein glycosylation patterns in AD, and especially introduced the latest progress on the mechanism of protein glycosylation affecting the progression of AD and the potential application of protein glycosylation in AD detection and treatment, thereby providing a wide range of opportunities for uncovering the pathogenesis of AD and promoting the translation of glycosylation research into future clinical applications.

Reelin Signaling in Neurodevelopmental Disorders and Neurodegenerative Diseases

“…In primary cultures, Aβ treatment is associated with impaired Reelin signaling leading to Reelin being less capable of down-regulating tau phosphorylation via Dab1 and Glycogen synthase kinase-3 beta (GSK3β) kinase [113]. This may be due to alterations in Reelin processing and glycosylation [100,103,114] or the inefficiency of Reelin to form active homodimers and, thus, its reduced ability to bind efficiently to its receptor, ApoER2 [113]. Recent studies also showed that the overexpression of Reelin in a mouse model of tauopathy (TgRln/VLW mice) led to a reduction in tau phosphorylation independently of the total tau, together with an improvement in LTP and cognition [115].…”

N-Glycosylation as a Modulator of Protein Conformation and Assembly in Disease

“…It thus comes as no surprise that defects in protein glycosylation are associated with a variety of diseases. We direct the reader to excellent reviews on glycosylation in cancer [ 43 , 44 , 45 , 46 , 47 , 48 ], neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, autism spectrum disorder, and schizophrenia [ 49 , 50 , 51 ], congenital disorders [ 52 , 53 ], infection, and inflammation [ 54 , 55 , 56 , 57 , 58 ]. To understand how the nature and conformation of the glycan can drastically change the interaction of a protein with another in the context of health and disease, we direct the reader to several review articles [ 47 , 59 , 60 , 61 ].…”

N-glycosylation as a Modulator of Protein Conformation and Assembly in Disease

“…It thus comes as no surprise that defects in protein glycosylation are associated with a variety of diseases. We direct the reader to excellent reviews on glycosylation in cancer [43][44][45][46][47][48], neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, autism spectrum disorder, and schizophrenia [49][50][51], congenital disorders [52,53], infection, and inflammation [54][55][56][57][58]. To understand how the nature and conformation of the glycan can drastically change the interaction of a protein with another in the context of health and disease, we direct the reader to several review articles [47,[59][60][61].…”