Treatment of tauopathies

Abstract

A method of treating tauopathies in a subject by administering the full length isomer 2 of p38 [gamma] or a constitutive active mutant p38 [gamma] D179A thereof. The phosphorylation of threonine in the tau sequence SSPGSPGTPGSRSR is promoted, and the phosphorylation is equivalent to threonine (T205) at the 205th amino acid of human tau. The method further comprises the introduction of a phosphoric acid mimetic of a phosphorylated tau, wherein the phosphorylated tau has been phosphorylated at the threonine in the tau sequence SSPGSPGTPGSRSR. The treatment method can improve the cognitive ability of a subject suffering from cognitive impairment associated with tauopathy, and reduce tau aggregation and neurofibrillary tangles.

Description

technical field [0001] The present invention relates to methods of treating tauopathies in subjects, methods of improving cognitive performance in subjects with cognitive impairment associated with tauopathies, methods of reducing tau aggregates and neurofibrillary tangles, and Compositions and formulations for such methods. Background technique [0002] Tau protein (also referred to herein as tau) is a highly soluble protein that is normally abundant in the central nervous system. Under healthy conditions, tau is associated with and stabilizes microtubules, especially those of nerve cells. [0003] Tauopathies are a class of progressive neurodegenerative diseases whose pathology is defined as the presence of abnormal accumulations of hyperphosphorylated tau in brain neuronal cells. Abnormal aggregation occurs when tau becomes hyperphosphorylated, dissociates from microtubules, and forms insoluble aggregates. As tau aggregates accumulate in neuronal cells, they form neuro...

AI Technical Summary

Problems solved by technology

[0006] To date, treatment options for tauopathies are limited after tau aggregation has occurred (e.g., advanced AD (i.e., with tau aggregates) or tauopathies associated only with tau aggregation)

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