Enhancing autophagy in Alzheimer's disease through drug repositioning.

Alzheimer's disease (AD) is one of the biggest human health threats due to increases in aging of the global population. Unfortunately, drugs for treating AD have been largely ineffective. Interestingly, downregulation of macroautophagy (autophagy) plays an essential role in AD pathogenesis. Therefore, targeting autophagy has drawn considerable attention as a therapeutic approach for the treatment of AD. However, developing new therapeutics is time-consuming and requires huge investments. One of the strategies currently under consideration for many diseases is "drug repositioning" or "drug repurposing". In this comprehensive review, we have provided an overview of the impact of autophagy on AD pathophysiology, reviewed the therapeutics that upregulate autophagy and are currently used in the treatment of other diseases, including cancers, and evaluated their repurposing as a possible treatment option for AD. In addition, we discussed the potential of applying nano-drug delivery to neurodegenerative diseases, such as AD, to overcome the challenge of crossing the blood brain barrier and specifically target molecules/pathways of interest with minimal side effects.

In Situ Growth of Metal-Organic Framework HKUST-1 on Graphene Oxide Nanoribbons with High Electrochemical Sensing Performance in Imatinib Determination.

Metal-organic frameworks (MOFs) have been previously investigated as electrode materials for developing electrochemical sensors. They have usually been reported to suffer from poor conductivity and improvement in the conductivity of MOFs is still a great challenge. Here, we reported the fabrication of an electrochemical sensor based on the in situ growth of framework HKUST-1 on conductive graphene oxide nanoribbons (GONRs)-modified glassy carbon electrode (GCE) (HKUST-1/GONRs/GCE). The as-fabricated modified electrode was characterized using field emission scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM, Fourier transform infrared, X-ray diffraction, electrochemical impedance spectroscopy, cyclic voltammetry, and Raman spectroscopy. The voltammetric response of HKUST-1/GONRs/GCE toward Imatinib (IMA), as an anticancer drug, is dramatically higher than HKUST-1/GCE because of the synergic effect of the GONRs and HKUST-1 framework. The calibration curve at the HKUST-1/GONRs/GCE for IMA covered two linear dynamic ranges, 0.04-1.0 and 1.0-80 µmol L-1, with a detection limit of 0.006 µmol L-1 (6 nmol L-1). Taking advantage of the conductivity of GONRs and large surface area of HKUST-1, a sensitive modified electrode was developed for the electrochemical determination of IMA. The present method provides an effective strategy to solve the poor conductivity of the MOFs. Finally, the obtained electrochemical performance made this modified electrode promising in the determination of IMA in urine and serum samples.