ABSTRACT
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-ß (Aß) peptide and, in the case of 5XFAD mice, reduces Aß 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.
Subject(s)
Alzheimer Disease/drug therapy , Disease Models, Animal , HSP70 Heat-Shock Proteins/therapeutic use , Administration, Intranasal , Alzheimer Disease/etiology , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/genetics , Amyloidogenic Proteins/metabolism , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Humans , In Vitro Techniques , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mutation/genetics , Olfaction Disorders/complications , Olfactory Bulb/injuries , Presenilin-1/geneticsABSTRACT
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.
