A Simple Model to Study Tau Pathology

Abstract

Tau proteins play a role in the stabilization of microtubules, but in pathological conditions, tauopathies, tau is modified by phosphorylation and can aggregate into aberrant aggregates. These aggregates could be toxic to cells, and different cell models have been used to test for compounds that might prevent these tau modifications. Here, we have used a cell model involving the overexpression of human tau in human embryonic kidney 293 cells. In human embryonic kidney 293 cells expressing tau in a stable manner, we have been able to replicate the phosphorylation of intracellular tau. This intracellular tau increases its own level of phosphorylation and aggregates, likely due to the regulatory effect of some growth factors on specific tau kinases such as GSK3. In these conditions, a change in secreted tau was observed. Reversal of phosphorylation and aggregation of tau was found by the use of lithium, a GSK3 inhibitor. Thus, we propose this as a simple cell model to study tau pathology in nonneuronal cells due to their viability and ease to work with.

High specificity of widely used phospho-tau antibodies validated using a quantitative whole-cell based assay

“…We were unable to determine Φ values for AT100, due to lack of binding to tau expressed in HEK293FT cells. Endogenous kinases in HEK293FT cells phosphorylate human tau (Camero et al 2014;Houck et al 2016). We showed that co-transfection of tau with GSK-3β led to increased phosphorylation of tau, but not for the AT100 target site (Thr212/Ser214).…”

“…Previous reports indicated that endogenous tau expression is undetected in HEK293 cells (Kfoury et al 2012;Liu et al 2013). In addition, when transfected with human tau, endogenous kinases in HEK293FT cells phosphorylated human tau (Camero et al 2014;Houck et al 2016). Leveraging these facts, we developed a ratiometric assay to quantify the specificity of phospho-tau antibodies (Fig.…”

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

“…Tauopathy is initiated by forming neurofibrillary tangles, neuritic plaques, and neuropil threads [40]. Excessive phosphorylation of tau has also been shown to contribute to tangle formation [41] and prevents neuronal cell function. In AD, brain synapses are disrupted by the Aβ plaques and tau tangles, damaged neurons die.…”

Circular RNA Encoded Amyloid Beta peptides—A Novel Putative Player in Alzheimer’s Disease

“…We demonstrated that circAβ-a serves as a template for the synthesis of a novel Aβ-containing polypeptide variant. Notably, the resulting product is further processed into Aβ peptides in human embryonic kidney 293 (HEK293) cells, which represents a well-established cellular model in AD research [ 61 , 62 ].…”