Tau immunotherapy in Alzheimer's disease and progressive supranuclear palsy.

Abstract

Tubulin-associated unit (tau) has been associated with more than 25 neurological disorders-the so-called tauopathies. Hence, finding a novel therapeutic agent targeting tau to halt the progression of diseases has been of interest. Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) are the most studied tauopathies. AD is characterized by two cardinal pathological mechanisms: amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs), leading to atrophy of the brain. Over the last few years, attention has been on NFTs composed of the hyperphosphorylated microtubule-associated protein tau. Tau contributes to the synaptic plasticity of axons; hyperphosphorylated and aggregated tau have been shown to increase the likelihood of cognitive impairments. PSP is also associated with tau accumulation in NFTs and neuropil threads, making this condition a candidate for tau-targeted therapies. Many tau-targeting therapies have been developed, and clinical trials are being conducted. Tau-targeting drugs are classified into four subgroups based on the pathological target: tau phosphorylation inhibitors, stabilizers of microtubules, enhancing tau clearance, and tau aggregation inhibitors. On the other hand, the desired specificity and sensitivity of tau immunotherapy agents without interrupting normal proteome are the fundamental point of tremendous attention. Starting with animal studies of these therapies to clinical trials, both are divided into passive and active immunotherapies, while passive immunotherapies are the method of desire. Targeting aggregation and phosphorylation sites of tau is the chief target of therapies. This article reviews the latest animal and clinical studies of tau-based immunotherapies and tau-targeted drugs for AD and PSP.