Apolipoprotein E (ApoE) peptide regulates tau phosphorylation via two different signaling pathways

Wang, Xiao‐Shu; Luebbe, Patricia; Gruenstein, Eric; Zemlan, Frank P.

doi:10.1002/(sici)1097-4547(19980301)51:5<658::aid-jnr13>3.0.co;2-z

Cited by 33 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One possibility is a predisposition created by the patient's apolipoprotein E (ApoE) genotype: the ApoE4 allele is associated with an increased risk of Alzheimer's disease [4,5,22]. ApoE isoforms are believed to directly interact with tau protein and affect both the latter's phosphorylation status and tendency to aggregate as neurofibrillary tangles [6,10,32,34].…”

Section: Introductionmentioning

confidence: 99%

Tau‐associated neuropathology in ganglion cell tumours increases with patient age but appears unrelated to ApoE genotype

Brat

Gearing

Goldthwaite³

et al. 2001

Neuropathology Appl Neurobio

View full text Add to dashboard Cite

Ganglion cell tumours, including gangliogliomas and gangliocytomas, are low grade neoplasms with a mature neuronal component. Ganglion cells within these lesions occasionally exhibit neurodegenerative changes including neurofibrillary tangles (NFT) similar to those in Alzheimer's disease. The frequency and spectrum of degenerative pathology in these lesions have not been defined, nor has their relation to patient age or factors such as apolipoprotein E (ApoE) genotype that predispose to Alzheimer's disease. We studied 72 ganglion cell tumours (61 gangliogliomas, 11 gangliocytomas) from patients 7 months to 72-years-old. Haematoxylin and eosin (H&E), silver stains (Hirano method) and immunohistochemistry for tau, alpha-synuclein and beta-amyloid were performed on formalin-fixed, paraffin-embedded tissue from surgical specimens. Tau-and silver-positive NFT and neuropil threads (NPT) were present in four of 26 ganglion cell tumours from patients over 30-years-old (ages 31, 38, 50, and 58 years). Neuronal granulovacuolar degeneration (GVD) was noted in five of 26 tumours from patients over 30-years-old (mean, 48 years). NFT, NPT, and GVD were not seen in ganglion cell tumours from patients under 30-years-old[0/46]. Cytoplasmic argentophilic bodies distinct from NFT were present in five of 26 tumours from patients over 30-years-old and in two of 46 under 30 years. Neither alpha-synuclein positive neuronal inclusions nor beta-amyloid immunoreactivity was noted in ganglion cell tumours from any age group. The distribution of ApoE genotypes was similar among those tumours that contained tau-associated neuropathology and those that did not. Neurodegenerative changes are uncommon in ganglion cell tumours, but increase in frequency with patient age. GVD, tau-positive NFT and NPT, and argentophilic bodies occur more often in ganglion cell tumours from patients over 30-yrs-old, but do not appear to be associated with a specific ApoE genotype.

show abstract

Section: Introductionmentioning

confidence: 99%

Tau‐associated neuropathology in ganglion cell tumours increases with patient age but appears unrelated to ApoE genotype

Brat

Gearing

Goldthwaite³

et al. 2001

Neuropathology Appl Neurobio

View full text Add to dashboard Cite

show abstract

“…pTau Thr231 is a known marker for AD (Buerger et al, 2003, 2006), which correlates with the neurofibrillary tangle burden in the brain of AD patients (Buerger et al, 2006). Tau phosphorylated at threonine 231 is dependent on activity of GSK3β following priming by Cdk5 (Sengupta et al, 1997; Wang et al, 1998; Platner et al, 2006). PLTP significantly reduced levels of pTau Thr231 (by approximately 55%, 65%, and 80% at 2, 5, and 10 μg/ml rPLTP, respectively; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Activation of the PI3K pathway is elicited through a ligand binding to receptors on the cell membrane, and two well‐defined pathways involved in the PI3K‐mediated regulation of GSK3β have been reported. One involves binding of apoE or Reelin to the apoE receptors APOER2 or VLDLR and consequent tyrosine phosphorylation of Disabled‐1 (Dab1) by an Src‐homology kinase, Fyn (Wang et al, 1998; Hiesberger et al, 1999; Howell et al, 1999a, b; Ohkubo et al, 2003; Brich et al, 2003; Hampel et al, 2004; Hoe et al, 2006). Phosphorylated Dab1 activates the PI3K pathway, leading to reduced activity of GSK3β and reduced tau phosphorylation (references given above).…”

Section: Resultsmentioning

confidence: 99%

Phospholipid transfer protein reduces phosphorylation of tau in human neuronal cells

Dong

Albers

Vuletic

2009

J of Neuroscience Research

View full text Add to dashboard Cite

Tau function is regulated by phosphorylation, and abnormal tau phosphorylation in neurons is one of the key processes associated with development of Alzheimer's disease and other tauopathies. In this study we provide evidence that phospholipid transfer protein (PLTP), one of the main lipid transfer proteins in the brain, significantly reduces levels of phosphorylated tau, and increases levels of the inactive form of glycogen synthase kinase-3β (GSK3β) in HCN2 cells. Furthermore, inhibition of the phosphatidylinositol-3 kinase (PI3K) reversed the PLTP-induced increase in levels of GSK3β phosphorylated at serine 9 (pGSK3β Ser9 ) and partially reversed the PLTP-induced reduction in tau phosphorylation. We provide evidence that the PLTP-induced changes are not due to activation of Disabled-1 (Dab1), since PLTP reduced levels of total and phosphorylated Dab1 in HCN2 cells. We have also shown that inhibition of tyrosine kinase activity of insulin receptor (IR) and/or insulinlike growth factor 1 (IGF1) receptor (IGFR) reverses PLTP-induced increase in levels of phosphorylated Akt (pAkt Thr308 and pAkt Ser473 ), suggesting that PLTP-mediated activation of the PI3K/Akt pathway is dependent on IR/IGFR receptor tyrosine kinase activity. Our study suggests that PLTP may be an important modulator of signal transduction pathways in human neurons.

show abstract

“…Apo E's action to alter select gene expression may not be restricted to the ovary. Evidence from other physiologic and pathologic situations where apo E is made locally, such as in the brain and within the vessel wall, suggests that apo E may influence lesion development via noncholesterol transport-dependent functions in diseases such as atherosclerosis and Alzheimer's disease [42][43][44][45].…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E Peptide Stimulation of Rat Ovarian Theca Cell Androgen Synthesis Is Mediated by Members of the Low Density Lipoprotein Receptor Superfamily1

Zerbinatti

Dyer

1999

Biology of Reproduction

View full text Add to dashboard Cite

Ovarian androgen production is rate limiting for follicular maturation and can induce follicular atresia. Thus, it is important to define the actions of the intraovarian agents, such as apolipoprotein (apo) E, that modulate theca cell androgen production. Theca cell androgen production is stimulated at low concentrations and inhibited at higher concentrations of native apo E. The apo E peptide, acetyl-Y(LRKLRKRLLRDADDL)(2)C or acetyl-Y(141-155)(2)C, has low density lipoprotein (LDL) receptor and LDL receptor-related protein-binding activity, and it mimics the activity of native apo E in the theca-interstitial cell system. To define the role of members of the LDL receptor superfamily in the apo E peptide-mediated responses, we found that receptor-associated protein prevented the stimulation without altering the inhibition of androstenedione production. The apo E peptide (129-162), which has no LDL receptor-binding activity, did not stimulate androstenedione production. The apo E peptide acetyl-Y(141-155)(2)C did not stimulate androstenedione production when cell surface heparan sulfate proteoglycans were degraded with heparinase. The apo E peptide acetyl-Y(141-155)(2)C bound to heparin, a property of LDL receptor ligands, and in this complex the peptide had no effect on androstenedione production. These observations support the conclusion that apo E-mediated stimulation, but not inhibition, of ovarian theca cell androstenedione production was mediated by members of the LDL receptor superfamily.

show abstract

Apolipoprotein E (ApoE) peptide regulates tau phosphorylation via two different signaling pathways

Cited by 33 publications

References 27 publications

Tau‐associated neuropathology in ganglion cell tumours increases with patient age but appears unrelated to ApoE genotype

Tau‐associated neuropathology in ganglion cell tumours increases with patient age but appears unrelated to ApoE genotype

Phospholipid transfer protein reduces phosphorylation of tau in human neuronal cells

Apolipoprotein E Peptide Stimulation of Rat Ovarian Theca Cell Androgen Synthesis Is Mediated by Members of the Low Density Lipoprotein Receptor Superfamily1

Contact Info

Product

Resources

About