TNAP upregulation is a critical factor in Tauopathies and its blockade ameliorates neurotoxicity and increases life-expectancy

Álvaro Sebastián-Serrano
Complutense University of Madrid
January 1, 2022
Neurobiol Dis
https://pubmed.ncbi.nlm.nih.gov/35065251

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/35065251

Research summary

This study investigates the role of tissue-nonspecific alkaline phosphatase (TNAP) in tauopathies. Researchers observed that TNAP is upregulated in the brains of Alzheimer's and Pick's disease patients, as well as in P301S tau transgenic mice. Genetic reduction of TNAP (haploinsufficiency) in P301S mice led to decreased neuronal hyperactivity, reduced brain atrophy, and improved survival. Pharmacological inhibition of TNAP with levamisole also ameliorated neurotoxicity and extended lifespan in these mice.

Key outcome of the study

TNAP upregulation contributes to tau-induced neurotoxicity; its genetic or pharmacological inhibition reduces neurodegeneration and extends lifespan in tauopathy models.

Model

P301S tau transgenic mice with TNAP haploinsufficiency (TNAP+/−) and P301S mice treated with the TNAP inhibitor levamisole to assess the impact of TNAP activity on tauopathy progression.

TARGET:
Alpl
TNAP, Tissue-nonspecific alkaline phosphatase

Keywords

Neurodegeneration, Tauopathies, Alzheimer's disease, TNAP inhibition, Therapeutic intervention

Technical specifications

Transgenic model, Haploinsufficiency, Pharmacological inhibition, P301S tauopathy model

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