Alzheimer's disease and other dementias are a class of neurodegenerative diseases, which are linked to the abnormal accumulations of the Tau protein in the brain. These brain disorders are one of the major reason of death and disability in old people worldwide. However, the therapeutic options are limited. (CUSABIO offers numerous proteins. )Now, a new study, led by researchers at University of Cambridge and Hungarian Academy of Sciences, provided a new treatment strategy for these diseases. The study appears in the Current Alzheimers Research.
The researchers targeted the monomeric Tau protein by using small molecule drugs to keep the protein's native function and decrease its misfolding and aggregation, which is associated with the progression of these disorders.
It is difficult to use small molecules to target the Tau protein, because it's an intrinsically disordered protein (IDP) that lacks stable 3D structure. To address the problem, the researchers used a special binding screening methodology to examine the binding between small molecules and Tau. As a result, the researchers found a host of new fragment and lead-like small molecules that are able to bind Tau. Moreover, some of the small molecules decreased the accumulations of Tau in a cellular model of Tauopathies.
The researchers were the first to show that monomeric Tau could be a potential receptor of small molecule drugs. In addition, the study brought the possibility of the therapeutic drugs to target early phases of the aggregation pathway of Tau and potentially other IDPs by small molecules.
They noted that the presented drug discovery paradigm has general applicability. It might be used to treat other disorders linked to toxic misfolded protein species.