ABSTRACT
Macroautophagy and chaperone-mediated autophagy (CMA) are two important subtypes of autophagy that play a critical role in cellular quality control under physiological and pathological conditions. Despite the marked differences between these two autophagic pathways, macroautophagy and CMA are intimately connected with each other during the autophagy-lysosomal degradation process, in particular, in the setting of neurological illness. Macroautophagy serves as a backup mechanism to removal of malfunctioning proteins (i.e., aberrant α-synuclein) from the cytoplasm when CMA is compromised, and vice versa. The molecular mechanisms underlying the conversation between macroautophagy and CMA are being clarified. Herein, we survey current overviews concentrating on the complex interactions between macroautophagy and CMA, and present therapeutic potentials through utilization and manipulation of macroautophagy-CMA crosstalk in the treatment of neurological diseases.
Subject(s)
Autophagy/physiology , Neurodegenerative Diseases/therapy , Amino Acid Motifs , Animals , Consensus Sequence , Cytosol/metabolism , HSC70 Heat-Shock Proteins/physiology , Humans , Intracellular Membranes/physiology , Intracellular Membranes/ultrastructure , Lysosomes/physiology , Lysosomes/ultrastructure , Membrane Fusion , Molecular Targeted Therapy , Phagosomes/physiology , Protein Aggregates , Protein Transport , Proteolysis , Vacuoles/physiology , Vesicular Transport Proteins/physiologyABSTRACT
Astragaloside IV, one of the main effective components isolated from Astragalus membranaceus, has multiple neuroprotective properties, while the effects of astragaloside IV on the attenuation of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) and its possible mechanisms are unknown. In the present study, we aimed to determine whether astragaloside IV could inhibit oxidative stress, reduce neuronal apoptosis, and improve neurological deficits after experimental SAH in rats. Rats (n=68) were randomly divided into the following groups: Sham group, SAH group, SAH+vehicle group, and SAH+astragaloside IV group. Astragaloside IV or an equal volume of vehicle was administered at 1 h and 6 h after SAH, all the rats were subsequently sacrificed at 24 h after SAH. Mortality, neurological scores, and brain edema were assessed, biochemical tests and histological studies were also performed at that point. SAH induced an increase in the malondialdehyde (MDA) level, neuronal apoptosis, cleaved caspase 3, brain edema and decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Astragaloside IV treatment reversed these changes and improved neurobehavioral outcomes of SAH rats. Our findings suggested that astragaloside IV may alleviate EBI after SAH through antioxidative and anti-apoptotic effects.
