A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis.

Greenberg, Sharon G.; Davies, Peter

doi:10.1073/pnas.87.15.5827

Cited by 648 publications

(434 citation statements)

References 30 publications

Supporting

Mentioning

424

Contrasting

Unclassified

Order By: Relevance

“…Sarcosyl insoluble tau was isolated from brain tissues of 3-12 months old rats based on the modified method of Greenberg and Davies [20]. Approximately 2 g of brain tissue was homogenized in 10 volumes of buffer (10 mM Tris, 0.8 M NaCl, 1 mM EGTA and 10% sucrose, pH 7.4) and centrifuged at 27 200 · g for 20 min.…”

Section: Extraction Of Sarcosyl Insoluble Taumentioning

confidence: 99%

Truncated tau from sporadic Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo

Žilka¹,

Filipčík²,

Koson³

et al. 2006

FEBS Letters

225

203

View full text Add to dashboard Cite

Truncated tau protein is the characteristic feature of human sporadic Alzheimer's disease. We have identified truncated tau proteins conformationally different from normal healthy tau. Subpopulations of these structurally different tau species promoted abnormal microtubule assembly in vitro suggesting toxic gain of function. To validate pathological activity in vivo we expressed active form of human truncated tau protein as transgene, in the rat brain. Its neuronal expression led to the development of the neurofibrillary degeneration of Alzheimer's type. Furthermore, biochemical analysis of neurofibrillary changes revealed that massive sarcosyl insoluble tau complexes consisted of human Alzheimer's tau and endogenous rat tau in ratio 1:1 including characteristic Alzheimer's disease (AD)-specific proteins (A68). This work represents first insight into the possible causative role of truncated tau in AD neurofibrillary degeneration in vivo.

show abstract

Section: Extraction Of Sarcosyl Insoluble Taumentioning

confidence: 99%

Truncated tau from sporadic Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo

Žilka¹,

Filipčík²,

Koson³

et al. 2006

FEBS Letters

225

203

View full text Add to dashboard Cite

show abstract

“…Tau protein isolation and analysis-Isolation of sarkosyl-insoluble tau was carried out as described by (Goedert et al, 1993), modified from (Greenberg & Davies, 1990). Brain tissue was homogenised in 10x volume (w/v) homogenisation buffer (10mM Tris-HCl pH 7.4, 0.8M NaCl, 1mM EGTA and 10% sucrose containing Complete protease inhibitor cocktail (Roche, Burgess Hill, UK).…”

Section: Protein Chemistrymentioning

confidence: 99%

Clinical and pathological features of an Alzheimer's disease patient with the MAPT ΔK280 mutation

Momeni

Pittman²,

Lashley³

et al. 2009

Neurobiology of Aging

View full text Add to dashboard Cite

We identified a case of Alzheimer's disease with a deletion of the lysine residue at codon 280 (ΔK280) in exon 10-encoded microtubule-binding repeat domain of the tau gene (MAPT). This mutation was originally identified in a sporadic case of frontotemporal dementia (FTD) with a family history of Parkinson's disease. In the original report, the authors were careful in their assessment of the pathogenicity and suggested one could not be sure whether the mutation was pathogenic or not. The mutation has always presented a conundrum because it is the only known mutation, of assumed pathogenicity, which increases the proportion of 3-repeat tau mRNA in in vitro assays. Here we present the clinical and pathological features of a new case with this mutation and discuss whether the mutation is indeed pathogenic.

show abstract

“…For immunoblotting samples were diluted directly into 2· SDS buffer and samples were electrophoresed on 10% SDS polyacrylamide gels and transferred to nitrocellulose membranes and blotted as above. To evaluate the phosphorylation of tau, the following phosphate-dependent antibodies were used: Tau-1 (a gift from Dr L. Binder), which recognizes a dephosphorylated epitope between residues 189 and 207 (Binder et al 1985;Szendrei et al 1993) and, PHF-1 (a gift from Dr P. Davies) which recognizes tau phosphorylated at Ser396/ 404 (Greenberg and Davies 1990;Otvos et al 1994) (numbering based on longest human isoform (Goedert et al 1989)). Total tau levels were determined using the combination of phospho-independent antibodies of Tau-5 (a gift from Dr L. Binder) (Carmel et al 1996) and 5A6 (Johnson et al 1997).…”

Section: Immunoprecipitation and Immunoblottingmentioning

confidence: 99%

Axin negatively affects tau phosphorylation by glycogen synthase kinase 3β

Stoothoff¹,

Bailey²,

Mi³

et al. 2002

Journal of Neurochemistry

View full text Add to dashboard Cite

Glycogen synthase kinase 3b (GSK3b) is an essential protein kinase that regulates numerous functions within the cell. One critically important substrate of GSK3b is the microtubuleassociated protein tau. Phosphorylation of tau by GSK3b decreases tau-microtubule interactions. In addition to phosphorylating tau, GSK3b is a downstream regulator of the wnt signaling pathway, which maintains the levels of b-catenin. Axin plays a central role in regulating b-catenin levels by bringing together GSK3b and b-catenin and facilitating the phosphorylation of b-catenin, targeting it for ubiquitination and degradation by the proteasome. Although axin clearly facilitates the phosphorylation of b-catenin, its effects on the phosphorylation of other GSK3b substrates are unclear.Therefore in this study the effects of axin on GSK3b-mediated tau phosphorylation were examined. The results clearly demonstrate that axin is a negative regulator of tau phosphorylation by GSK3b. This negative regulation of GSK3b-mediated tau phosphorylation is due to the fact that axin efficiently binds GSK3b but not tau and thus sequesters GSK3b away from tau, as an axin mutant that does not bind GSK3b did not inhibit tau phosphorylation by GSK3b. This is the first demonstration that axin negatively affects the phosphorylation of a GSK3b substrate, and provides a novel mechanism by which tau phosphorylation and function can be regulated within the cell.

show abstract

A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis.

Cited by 648 publications

References 30 publications

Truncated tau from sporadic Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo

Truncated tau from sporadic Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo

Clinical and pathological features of an Alzheimer's disease patient with the MAPT ΔK280 mutation

Axin negatively affects tau phosphorylation by glycogen synthase kinase 3β

Contact Info

Product

Resources

About