NAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model

Shiryaev, Natalia; Jouroukhin, Yan; Giladi, Eliezer; Polyzoidou, Eleni; Grigoriadis, Nikolaos; Rosenmann, Hanna; Gozes, Illana

doi:10.1016/j.nbd.2009.02.011

Cited by 115 publications

(81 citation statements)

References 28 publications

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“…Another potential mechanism for the neuroprotective effects of both the glial-derived NPC transplant and the direct astrocytes may be through secretion of activity-dependent neuroprotective protein (ADNP). Recent literature suggests this protein is secreted by astrocytes, while intranasal delivery of a peptide fragment derived from ADNP, termed NAP, has been demonstrated to increase soluble tau, reduce hyperphosphorylation, and reduce cognitive decline observed in tau transgenic mice (Furman et al, 2004;Shiryaev et al, 2009). This mechanism may be an additional effect that the exogenous transplanted astrocytes have on the endogenous populations and thus promotes neuroprotection.…”

Section: Discussionmentioning

confidence: 99%

Cell-Mediated Neuroprotection in a Mouse Model of Human Tauopathy

Hampton¹,

Webber²,

Bilican³

et al. 2010

J. Neurosci.

107

106

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Tau protein in a hyperphosphorylated state makes up the intracellular inclusions of several neurodegenerative diseases, including Alzheimer's disease and cases of frontotemporal dementia. Mutations in Tau cause familial forms of frontotemporal dementia, establishing that dysfunction of tau protein is sufficient to cause neurodegeneration and dementia. Transgenic mice expressing human mutant tau in neurons exhibit the essential features of tauopathies, including neurodegeneration and abundant filaments composed of hyperphosphorylated tau. Here we show that a previously described mouse line transgenic for human P301S tau exhibits an age-related, layer-specific loss of superficial cortical neurons, similar to what has been observed in human frontotemporal dementias. We also show that focal neural precursor cell implantation, resulting in glial cell differentiation, leads to the sustained rescue of cortical neurons. Together with evidence indicating that astrocyte transplantation may be neuroprotective, our findings suggest a beneficial role for glial cell-based repair in neurodegenerative diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Cell-Mediated Neuroprotection in a Mouse Model of Human Tauopathy

Hampton¹,

Webber²,

Bilican³

et al. 2010

J. Neurosci.

107

106

View full text Add to dashboard Cite

show abstract

“…number 23225). This approach only extracts detergent soluble tau protein but not tau protein aggregated in NFT (24). The brain supernatant (1:10 000 dilution) and CSF (1:50 dilution) were used to measure tau protein using a human total tau Elisa kit according to the manufacturer's instruction (ThermoFisher Scientific Inc., Cat.…”

Section: Tissue Processing and Biochemical Assaymentioning

confidence: 99%

A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor

Han

Serrano

Beach

et al. 2017

J Neuropathol Exp Neurol

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Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previously been quantified. We measured CSF tau and soluble brain tau at autopsy in temporal and frontal brain tissue samples from 7 cognitive normal, 12 mild cognitively impaired, and 19 AD subjects. Based on the measured brain soluble tau, we calculated the whole brain tau load and estimated tau secretion factor. Our results suggest that the increase in NFT in AD is likely attributable to post-translational processes; the increase in CSF tau in AD patients is due to an accelerated carrier-based secretion. Moreover, cognitive dysfunction assessed by final Mini-Mental State Examination scores correlated with the secretion factor but not with the soluble tau.

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“…We then demonstrated that partial ADNP deficiency (ADNP+/-) resulted in cognitive and social impairments that were coupled to tauopathy, a major pathology in Alzheimer's disease and frontotemporal dementia (Vulih-Shultzman et al 2007). In the ADNP-deficient model (Vulih-Shultzman et al 2007) as well as in models of Alzheimer's disease (Matsuoka et al 2007;Matsuoka et al 2008) and frontotemporal dementia (Shiryaev et al 2009), we showed that intranasal administration of NAP ameliorated spatial memory impairments and inhibited tau-related pathology. It is interesting to note that ADNP and its related protein ADNP2, proteins that are important for cellular viability (Kushnir et al 2008) are both expressed in the human hippocampus (Bassan et al 1999;Dresner et al 2010;Zamostiano et al 2001) that is associated with short-term memory and Alzheimer's disease pathology.…”

Section: Editorial: From the Desk Of The Editor-in-chiefmentioning

confidence: 54%

NAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model

Cited by 115 publications

References 28 publications

Cell-Mediated Neuroprotection in a Mouse Model of Human Tauopathy

Cell-Mediated Neuroprotection in a Mouse Model of Human Tauopathy

A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor

VIP–PACAP 2010: My Own Perspective on Modulation of Cognitive and Emotional Behavior

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