Brain deterioration resulting from "protein folding" diseases, such as the Alzheimer's disease (AD), is one of the leading causes of morbidity and mortality in the aging human population. Heat shock proteins (Hsps) constitute the major cellular quality control system for proteins that mitigates the pathological burden of neurotoxic protein fibrils and aggregates. However, the therapeutic effect of Hsps has not been tested in a relevant setting. Here we report the dramatic neuroprotective effect of recombinant human Hsp70 in the bilateral olfactory bulbectomy model (OBX mice) and 5XFAD mouse models of neurodegeneration. We show that intranasally-administered Hsp70 rapidly enters the afflicted brain regions and mitigates multiple AD-like morphological and cognitive abnormalities observed in model animals. In particular, in both cases it normalizes the density of neurons in the hippocampus and cortex which correlates with the diminished accumulation of amyloid-β (Aβ) peptide and, in the case of 5XFAD mice, reduces Aβ plaque formation. Consistently, Hsp70 treatment also protects spatial memory in OBX and 5XFAD mice. These studies demonstrate that exogenous Hsp70 may be a practical therapeutic agent for treatment of neurodegenerative diseases associated with abnormal protein biogenesis and cognitive disturbances, such as AD, for which neuroprotective therapy is urgently needed.
Terahertz time-domain spectroscopy (THz-TDS) was used to determine the spectra (range = 1.2-120 cm) of aqueous solutions of bovine serum albumin (BSA) at pH range 2.5-10. Under each of the selected pH, BSA molecules exist in a different conformation, compared to other pH values. The spectra were used to calculate the functions of the dielectric permittivity of BSA solutions. Dielectric functions of the aqueous phase of BSA solutions were calculated based on the Bruggeman model, without the contribution of BSA itself. Fitting of the dielectric functions was performed using a model which includes three water spectral bands: two relaxation bands with relaxation times of about 8.28 and 0.3 ps and a vibrational band with a maximum of about 180 cm. The parameters of these bands were determined through fitting and physical interpretation at the molecular level can be provided for each of them. A comparison between the values of model parameters of solutions with BSA and without BSA allowed to conclude that the main effect of BSA is the formation of strongly bound hydration shells in the immediate proximity to the protein molecule. At the same time, the structure of more distant layers of the hydration shells is destroyed, with an increased formation of free water molecules. Some differences are observed in the effect of different BSA conformations on the aqueous phase of solution. The proposed approach can be generalized and applied for studying of a wide class of biological macromolecules in aqueous solutions.
The absorption spectra of liquid water and various aqueous solutions were analyzed in a terahertz frequency domain (from 6 to 200 cm(-1)) which characterize the collective dynamics of water molecules. Particular attention was paid to the relaxation process in the range of ∼6-80 cm(-1). The physical essence of this process on the molecular level is still unclear. We found that the amplitude of this relaxation process correlates with the degree of destruction of water structure. The obtained data allowed us to interpret this process as a monomolecular relaxation of free water molecules. On the basis of a consideration of the water polarization in the electric field, we proposed a method of calculation of the amount of free water molecules in solution.
Phenomenon of autofluorescence from vegetative microspores of spore-breding plant Equisetum arvense has been studied by methods of laser-scanning confocal microscopy (LSCM) and microspectrofluorimetry during the development of the cells. The microspores have demonstrated a difference between structures: blue-fluorescing cover and red-fluorescing chloroplasts. The fluorescence spectra of the studied cells was also measured by original microspectrofluorimeter. The character of the spectra and the color of fluorescence was changed during the microspores germination. The red fluorescence of the microspores was, mainly, due to the presence of chlorophyll and azulenes. The unicellular microspores may be recommended as natural probes of cellular viability and development.
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