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Monosaccharides and Molecular Changes in Neurodegenerative Stress Conditions
Author(s) -
Mosetter Kurt,
Horstkorte Rüdiger,
Reutter Werner
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a687-a
Subject(s) - monosaccharide , enzyme , biochemistry , biosynthesis , cytosol , intracellular , serine , glucocerebrosidase , chemistry , threonine
By the work of G. Hart it could be shown that not only complex glycans but the attachement of a monosaccharide only plays a crucial role in regulating intracellular functions of proteins. He found that the monosaccharide N‐acetylglucosamine can be O‐glycosidically linked to serine/threonine to some nuclear or some cytosolic proteins modifying their activity, either during processes of transcription or of enzyme activities. The O‐GlcNAc‐ylation is mostly observed during metabolic stress situations of the cell. Our main interest lies in age‐related neurodegenerations like Parkinson¹s and Alzheimer¹s disease. With respect to Parkinson¹s disease it could be shown in PC12 cells that the key enzyme of L‐DOPA biosynthesis, the tyrosine‐3‐monooxygenase, is O‐GlcNAc‐ylated. By the administration of the novel mannosamine analogue, ‐propanoylmannosamine, the O‐GlcNAc‐ylation of the monooxygenase decreases and the L‐DOPA biosynthesis increases significantly (Horstkorte et al., in preparation). It is assumed that in Parkinson‐patients this enzyme is modified by O‐GlcNAc. So the application of the mannosamine analogue might be regarded as a therapeutic tool. In Alzheimer¹s disease O‐GlcNAc‐ylation of proteins is well described. Therefore, it may be hypothised that these analogues might be of benefit for those patients too, if further biochemical and toxicological studies may allow it.