Phosphorylated tau targeted small-molecule PROTACs for the treatment of Alzheimer's disease and tauopathies

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1867

Review

Pradeepkiran, Jangampalli Adi¹  Reddy, P. Hemachandra^1,2,3,4,5 

[1] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, 3601 4th St, Lubbock, TX 79430 USA

[2] Texas Tech Univ, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Lubbock, TX 79430 USA

[3] Texas Tech Univ, Hlth Sci Ctr, Dept Neurol, Lubbock, TX 79430 USA

[4] Texas Tech Univ, Hlth Sci Ctr, Grad Sch Biomed Sci, Dept Publ Hlth, Lubbock, TX 79430 USA

[5] Texas Tech Univ, Hlth Sci Ctr, Dept Speech Language & Hearing Sci, Lubbock, TX 79430 USA

关键词: Alzheimer's disease;    Tau protein;    Hyperphosphorylation;    Neurofibrillary tangles;    Paired helical filament;    PROTACs;    Tauopathies;   

DOI  :  10.1016/j.bbadis.2021.166162

来源: Elsevier

【 摘 要 】

Tau is a microtubule-stabilizing protein that plays an important role in the formation of axonal microtubules in neurons. Phosphorylated tau (p-Tau) has received great attention in the field of Alzheimer's disease (AD) as a potential therapeutic target due to its involvement with synaptic damage and neuronal dysfunction. Mounting evidence suggests that amyloid beta (A beta)-targeted clinical trials continuously failed; therefore, it is important to consider alternative therapeutic strategies such as p-tau-PROTACs targeted small molecules for AD and other tauopathies. The present article describes the characteristics of tau biology, structure, and function in both healthy and pathological states in AD. It also explains data from studies that have identified the involvement of ptau in neuronal damage and synaptic and cognitive functions in AD. Current article also covers several aspects, including small molecule inhibitors, and the development of p-tau-PROTACs targeted drug molecules to treat patients with AD and other tauopathies.

【 授权许可】

Free