Altered Glycosylation Pattern of Proteins in Alzheimer Disease

Abstract

Post-translational modifications due to glycosylation of proteins in human brains from patients with Alzheimer disease (AD) were analyzed using lectin histochemistry. Results indicate a significant increase in the production of O-glycosylated (containing Galbeta1,3GalNAc alpha1,0 Ser/Thr or GalNAc alpha1,0 Ser/Thr) proteins in neuritic plaques and neurofibrillary tangles which are the major histopathological hallmarks of AD brains. These alterations were determined by positive labelling with lectins obtained from Amaranthus leucocarpus (ALL) and Macrobrachium rosenbergii (MRL) respectively. Immunohistochemistry indicated that the lectin-staining labelled specifically both neurofibrillary tangles and neuritic plaques. In contrast, lectins labelling was restricted to microvessels in normal control brains. These results provide evidence that modifications of the specific glycosylation patterns are closely related with the presence of the hallmark lesions of this disease, suggesting that an abnormal enzymatic processing of proteins may be an early event in the neuronal degeneration which characterises AD.

Simultaneous Characterization of Glyco- and Phosphoproteomes of Mouse Brain Membrane Proteome with Electrostatic Repulsion Hydrophilic Interaction Chromatography

“…Such alteration is required for the induction of many forms of synaptic plasticity such as long term potentiation and depression in learning and memory formation. For example, aberrant glycosylation and abnormal phosphorylation have been found to be associated with many neurological disorders such as Alzheimer disease (7)(8)(9), Parkinson disease (10,11), Guillain-Barré and Miller-Fisher syndromes (12), and even muscle-eye-brain disease (13). Understanding the brain glyco-and phosphoproteomes is therefore not only essential for studying the biology of these diseases but also aiding drug discovery and translational research as many of the glycoproteins have the potential to be viable drug targets due to the ease of their accessibility on the cell surface.…”

Alteration of the sialylation pattern of the murine tooth germ after ethanol exposure

“…Glycoconjugates (glycoproteins or glycolipids) participate in important cellular functions associated with normal development, growth, communication, and survival (Jü rgen, 1987;Hennet and Ellies, 1999). Abnormalities in the expression of O-glycans are related to a number of biological functions that become altered in certain disorders, such as neurodegenerative diseases, immunological responses, and neoplasms (Guevara et al, 1998;Jiménez-Martínez et al, 2002).…”

“…Changes in the expression of specific sialic acids during differentiation may be useful markers for the degree of cell maturation (Sierra et al, 2001;Cerna et al, 2002). Changes in glycosylation have been observed in some congenital diseases (Aebi and Hennet, 2001;Martin-Rendon and Blake, 2003) and pathological processes, such as Alzheimer disease (Guevara et al, 1998), prion protein disease (Rudd et al, 2002), and cancer (Dennis et al, 1999).…”

Glycosylation Changes as Markers for the Diagnosis and Treatment of Human Disease

“…Besides the glycosylation changes to APP and proteases that process this protein, there is a significant increase in the overall production of O-glycosylated proteins in neuritic plaques and neurofibrillary tangles found in the brains ofAlzheimer's disease patients (Guevara et a/., 1998). Similar widespread changes in O-glycosylation have been linked to pathogenic changes in neuronal plasticity (Espinosa et ill., 200 I).…”