Photoswitchable Pseudoirreversible Butyrylcholinesterase Inhibitors Allow Optical Control of Inhibition in Vitro and Enable Restoration of Cognition in an Alzheimer's Disease Mouse Model upon Irradiation.

To develop tools to investigate the biological functions of butyrylcholinesterase (BChE) and the mechanisms by which BChE affects Alzheimer's disease (AD), we synthesized several selective, nanomolar active, pseudoirreversible photoswitchable BChE inhibitors. The compounds were able to specifically influence different kinetic parameters of the inhibition process by light. For one compound, a 10-fold difference in the IC50-values (44.6 nM cis, 424 nM trans) in vitro was translated to an "all or nothing" response with complete recovery in a murine cognition-deficit AD model at dosages as low as 0.3 mg/kg.

Exploring the Use of Intracranial and Extracranial (Remote) Photobiomodulation Devices in Parkinson's Disease: A Comparison of Direct and Indirect Systemic Stimulations.

In recent times, photobiomodulation has been shown to be beneficial in animal models of Parkinson's disease, improving locomotive behavior and being neuroprotective. Early observations in people with Parkinson's disease have been positive also, with improvements in the non-motor symptoms of the disease being evident most consistently. Although the precise mechanisms behind these improvements are not clear, two have been proposed: direct stimulation, where light reaches and acts directly on the distressed neurons, and remote stimulation, where light influences cells and/or molecules that provide systemic protection, thereby acting indirectly on distressed neurons. In relation to Parkinson's disease, given that the major zone of pathology lies deep in the brain and that light from an extracranial or external photobiomodulation device would not reach these vulnerable regions, stimulating the distressed neurons directly would require intracranial delivery of light using a device implanted close to the vulnerable regions. For indirect systemic stimulation, photobiomodulation could be applied to either the head and scalp, using a transcranial helmet, or to a more remote body part (e.g., abdomen, leg). In this review, we discuss the evidence for both the direct and indirect neuroprotective effects of photobiomodulation in Parkinson's disease and propose that both types of treatment modality, when working together using both intracranial and extracranial devices, provide the best therapeutic option.

Stability of an anti-stroke peptide: driving forces and kinetics in chemical degradation.

NR2B9c (Lys-Leu-Ser-Ser-Ile-Glu-Ser-Asp-Val) is a 9-amino acid peptide that has been illustrated to be a potential anti-stroke drug. For more effective treatment, suitable drug delivery systems should be developed. However, little is known about the stability of NR2B9c which is essential to its formulation. In this study, a reversed-phase high-performance liquid chromatography (HPLC) was applied to study the forced degradation behavior and stability of NR2B9c. HPLC studies were performed with an C8 column using a mobile phase consisting of acetonitrile (14.5:85.5, v/v) and aqueous solution (0.1% trifluoroacetic acid (TFA) and 0.05 M KH2PO4). The flow rate and the wavelength set during HPLC detection were 1.0 mL/min and 205 nm, respectively. The degradation pattern of NR2B9c aqueous solution followed pseudo first-order kinetics. The degradation rate at pH 7.5 was the slowest according to the plotting V-shaped pH-rate profile. The influence of temperature on the rate of reactions was interpreted in terms of Arrhenius equation (r(2)>0.98). Thermodynamic parameters were calculated based on Eyring equation (r(2)>0.98). The concentrations of drug, buffer species, buffer concentrations, oxidation and organic solvents have noticeable effects on the degradation of NR2B9c while ultrasound shows little impact under the experimental conditions. In a word, this study may give a detailed description of stability of NR2B9c.