title: Post-translational modifications of tau protein in Alzheimer's disease.
abstract: Microtubule-associated protein tau undergoes several post-translational modifications and aggregates into paired helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies. These modifications of tau include hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and proteolysis. Hyperphosphorylation and glycosylation are crucial to the molecular pathogenesis of neurofibrillary degeneration of AD. The others appear to represent failed mechanisms for neurons to remove damaged, misfolded, and aggregated proteins. This review summarizes the abnormal post-translational modifications of tau and discusses the pathophysiological relevance of hyperphosphorylation and glycosylation of tau. Total tau and phosphorylated tau levels in cerebrospinal fluid as a diagnostic biomarkers are also reviewed. Analyses of the current advances in tau modifications suggest that intervention addressing these abnormalities may offer promising therapeutic opportunities to prevent and treat neurofibrillary degeneration of AD and other tauopathies.
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. cxgong@ultinet.net
authors.forename: C-X
authors.initials: CX
authors.lastname: Gong
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: I
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: K
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D006031:Glycosylation; D006801:Humans; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016875:tau Proteins