Glycosaminoglycans and beta-amyloid, prion and tau peptides in neurodegenerative diseases.
Protein aggregation into dense filamentous inclusions is a characteristic feature of many etiologically diverse neurodegenerative disorders including Alzheimer's disease (AD), spongiform encephalopathies, and tauopathies. Thus, beta-amyloid peptide (Abeta) accumulates within senile amyloid plaques in AD, protease-resistant prion protein constitutes the amyloid deposits in spongiform encephalopathies and tau protein gives rise to neurofibrillary tangles (NFT) both in AD and in tauopathies. Curiously, these abnormal protein inclusions contain, in addition to their major peptide components, some associated sulfated glycosaminoglycans (sGAG). Here we discuss the proposal that the binding of sGAG to aggregate-forming peptides may modify the pathogenic process depending on their subcellular localization.
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Javier
J
Díaz-Nido
Francisco
F
Wandosell
Jesús
J
Avila
D000544:Alzheimer Disease / Q000209:etiology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000209:etiology*; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D006025:Glycosaminoglycans; D011328:Prions; D016875:tau Proteins