Investigation of the expression of Cis P-tau and Pin1 proteins following air pollution induction in the brain tissue of C57BL/6 mice.

Alzheimer's disease (AD) is a multifactorial disease in which environmental factors play a role. Among environmental factors, air pollution is a vital issue in modern life. Despite extensive considerations, it remains uncertain how pollution mediates neurodegeneration in AD. Beta-amyloids and hyperphosphorylated tau proteins are the two main pathological markers that have been studied in AD so far. Tau protein is basically a phosphoprotein whose functions are controlled by phosphorylation. The function of tau protein is to be located on the surface of microtubules and stabilize them. Studies have shown that phosphorylated tau protein (p-tau) exists in cis and trans conformations at Thr231, among which cis is highly neurotoxic. The Pin1 enzyme performs the conversion of cis to trans or vice versa. In this study, an experimental mouse model was designed to investigate the formation of cis p-tau by inducing air pollution. In this way, mice were randomly exposed to pollution at 2-week, 1-month, and 2-month intervals. We investigated the formation of phosphorylated cis tau form during air pollution on mouse brains using Western blots and immunofluorescence. The fluorescent imaging results and Western blotting analysis of mouse brains revealed a significant accumulation of cis p-tau in pollution-treated mice models compared to the healthy control mice. According to Western blot results, air pollution induction caused a significant decrease in Pin1 protein. The results clearly show that the tauopathy observed during air pollution is mediated through the formation of cis tau. Our findings unravel tauopathy mysteries upon pollution and would help find a possible therapeutic target to fight the devastating disorder caused by modern life.

Detection of receptor tyrosine kinase-orphan receptor-2 using an electrochemical immunosensor modified with electrospun nanofibers comprising polyvinylpyrrolidone, soy, and gold nanoparticles.

An electrochemical immunosensing platform was developed for the detection of receptor tyrosine kinase-orphan receptor-2 (ROR2) at a glassy carbon electrode (GCE) modified with the electrospun nanofiber containing polyvinylpyrrolidone (PVP), soy, and Au nanoparticles (AuNPs). The PVP/soy/AuNP nanofiber exhibited good electrochemical behavior due to synergistic effects between PVP, soy, and AuNPs. The PVP/soy in the modified film provided good mechanical strength, high porosity, flexible structures, and high specific surface area. On the other hand, the presence of AuNPs effectively improved conductivity, as well as the immobilization of anti-ROR2 on the modified GCE, leading to enhanced sensitivity. Various characterization approaches such as FE-SEM, FTIR, and EDS were used for investigating the morphological and structural features, and the elemental composition. The designed immunosensor performance was investigated using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV). Under optimum conditions with a working potential range from -0.2 to 0.6 V (vs. SCE), sensitivity, linear range (LR), limit of detection (LOD), and correlation coefficient (R2) were acquired at 122.26 µA/cm2 dec, 0.01-1000 pg/mL, 3.39 fg/mL, and 0.9974, respectively. Furthermore, the determination of ROR2 in human plasma samples using the designed immunosensing platform was examined and exhibited satisfactory results including good selectivity against other proteins, reproducibility, and cyclic stability.

Regulation of mitochondrial transport and inter-microtubule spacing by tau phosphorylation at the sites hyperphosphorylated in Alzheimer's disease.

The microtubule-associated protein Tau is a major component of the neurofibrillary tangles that serve as a neuropathological hallmark of Alzheimer's disease. Tau is a substrate for protein phosphorylation at multiple sites and occurs in tangles in a hyperphosphorylated state. However, the physiological functions of Tau phosphorylation or how it may contribute mechanistically to Alzheimer's pathophysiology are not completely understood. Here, we examined the function of human Tau phosphorylation at three sites, Ser199, Ser202, and Thr205, which together comprise the AT8 sites that mark abnormal phosphorylation in Alzheimer's disease. Overexpression of wild-type Tau or mutated forms in which these sites had been changed to either unphosphorylatable alanines or phosphomimetic aspartates inhibited mitochondrial movement in the neurite processes of PC12 cells as well as the axons of mouse brain cortical neurons. However, the greatest effects on mitochondrial translocation were induced by phosphomimetic mutations. These mutations also caused expansion of the space between microtubules in cultured cells when membrane tension was reduced by disrupting actin filaments. Thus, Tau phosphorylation at the AT8 sites may have meaningful effects on mitochondrial movement, likely by controlling microtubule spacing. Hyperphosphorylation of the AT8 sites may contribute to axonal degeneration by disrupting mitochondrial transport in Alzheimer's disease.

Tau Protein Biosensors in the Diagnosis of Neurodegenerative Diseases.

Tau protein plays a crucial role in diagnosing neurodegenerative diseases. However, performing an assay to detect tau protein on a nanoscale is a great challenge for early diagnosis of diseases. Enzyme-linked immunosorbent assay (ELISA), western-blotting, and molecular-based methods, e.g., PCR and real-time PCR, are the most widely used methods for detecting tau protein. These methods are subject to certain limitations: the need for advanced equipment, low sensitivity, and specificity, to name a few. With the above said, it is necessary to discover advanced and novel methods for monitoring tau protein. Counted among remarkable approaches adopted by researchers, biosensors can largely eliminate the difficulties and limitations associated with conventional methods. The main objective of the present study is to review the latest biosensors developed to detect the tau protein. Furthermore, the problems and limitations of conventional diagnosis methods were discussed in detail.

A possible mechanism for controlling processive transport by microtubule-associated proteins.

Molecular mechanisms of axonal transport have been evaluated by several investigators. It seems that microtubules (MTs) act as a track for the transport and microtubule-associated proteins (MAPs) seem to play as a regulating factor in it. In order to transport MTs must move in the radial direction to make room for a vesicle and when the cargo passes, return to the previous position for the maintenance of neuronal structure. An inhibitor factor against the radial movement is the steric constraints resulted from presence of MAPs. In fact, inter-microtubular spaces (IMS) in the neuronal processes are resulted from the space-making role of the MAPs. Since the IMS must be locally altered to make enough room for a vesicle, it seems relevant to imagine some mechanisms that control the steric constraints for an efficient vesicular transport. Here we juxtapose the older findings and the recent ones to investigate the possible effects of MAPs on the processive transport.