Exosomes derived from mesenchymal stem cells attenuate inflammation and demyelination of the central nervous system in EAE rats by regulating the polarization of microglia.

Autophagy, a conserved cellular degradation and recycling process, can be enhanced by nutrient depletion, oxidative stress or other harmful conditions to maintain cell survival. 6-Hydroxydopamine/ascorbic acid (6-OHDA/AA) is commonly used to induce experimental Parkinson’s disease (PD) lesions by causing oxidative damage to dopaminergic neurons. Activation of autophagy has been observed in the 6-OHDA-induced PD models. However, the mechanism and exact role of autophagy activation in 6-OHDA PD model remain inconclusive. In this study, we report that autophagy was triggered via mucolipin 1/calcium/calcineurin/TFEB (transcription factor EB) pathway upon oxidative stress induced by 6-OHDA/AA. Interestingly, overexpression of TFEB alleviated 6-OHDA/AA toxicity. Moreover, autophagy enhancers, Torin1 (an mTOR-dependent TFEB/autophagy enhancer) and curcumin analog C1 (a TFEB-dependent and mTOR-independent autophagy enhancer), significantly rescued 6-OHDA/AA-induced cell death in SH-SY5Y cells, iPSC-derived DA neurons and mice nigral DA neurons. The behavioral abnormality of 6-OHDA/AA-treated mice can also be rescued by Torin 1 or C1 administration. The protective effects of Torin 1 and C1 can be blocked by autophagy inhibitors like chloroquine (CQ) or by knocking down autophagy-related genes TFEB and ATG5. Taken together, this study supports that TFEB-mediated autophagy is a survival mechanism during oxidative stress and pharmacological enhancement of this process is a neuroprotective strategy against oxidative stress-associated PD lesions.

Pharmacological enhancement of TFEB-mediated autophagy alleviated neuronal death in oxidative stress-induced Parkinson's disease models.

Background Marine Enteromorpha polysaccharides (EPPs) have been reported to present various physiological and bioactivities based on their specific chemical structures, such as monosaccharide compositions and glycosidic linkages. Scope and approach However, the structure-activity relationship of Enteromorpha polysaccharides is mostly unknown. This review aims to provide a brief summary of structural, functional, and chemical characteristics of Enteromorpha polysaccharides. Key findings and conclusions Modified Enteromorpha polysaccharides have several powerful bioactive functions. Sulfated EPPs with lower molecular weights were found to exhibit excellent immune-relevant and antioxidant activities. Carboxymethylated, hydroxamated, phthaloyl, and acetylated derivatives also showed significantly enhanced antioxidant and antibacterial activities as well as moisture absorbing capacities. EPPs were considered as novel natural agents, exhibiting outstanding druggable effects compared with ordinary drugs. However, the structure-function relationships of them are yet to be clearly established. The purpose of this overview is focusing on the current advances in the structural characterization, biological activities and mechanisms of action of Enteromorpha polysaccharides.

Polysaccharides from Marine Enteromorpha: Structure and function

Schisandra chinensis (Turcz.) Baill. (SCE) is a plant with high potential for beneficial health effects, confirmed by molecular studies. Its constituents exert anti-cancer effects through the induction of cell cycle arrest and apoptosis, as well as inhibition of invasion and metastasis in cancer cell lines and experimental animals. SCE displays antimicrobial effects against several pathogenic strains. It has anti-diabetic potential, supported by hypoglycemic activity. A diet rich in SCE improves pancreatic functions, stimulates insulin secretion, and reduces complications in diabetic animals. SCE prevents lipid accumulation and differentiation of preadipocytes, indicating its anti-obesity potential. SCE exerts a protective effect against skin photoaging, osteoarthritis, sarcopenia, senescence, and mitochondrial dysfunction, and improves physical endurance and cognitive/behavioural functions, which can be linked with its general anti-aging potency. In food technology, SCE is applied as a preservative, and as an additive to increase the flavour, taste, and nutritional value of food. In summary, SCE displays a variety of beneficial health effects, with no side effects. Further research is needed to determine the molecular mechanisms of SCE action. First, the constituents responsible for its beneficial effects should be isolated and identified, and recommended as preventative nutritional additives, or considered as therapeutics.

https://www.mdpi.com/2072-6643/11/2/333/pdf

Potential of Schisandra chinensis (Turcz.) Baill. in Human Health and Nutrition: A Review of Current Knowledge and Therapeutic Perspectives.

Autophagy is a regulated, intracellular degradation process that delivers unnecessary or dysfunctional cargo to the lysosome. Autophagy has been viewed as an adaptive survival response to various stresses, whereas in other cases, it promotes cell death. Therefore, both deficient and excessive autophagy may lead to cell death. In this study, we specifically attempted to explore whether and how dysregulated autophagy contributes to caspase-dependent neuronal cell death induced by the neurotoxin 6-hydroxydopamine (6-OHDA). Ultrastructural and biochemical analyses indicated that MN9D neuronal cells and primary cultures of cortical neurons challenged with 6-OHDA displayed typical features of autophagy. Cotreatment with chloroquine and monitoring autophagic flux by a tandem mRFP-EGFP-tagged LC3 probe indicated that the autophagic phenomena were primarily caused by dysregulated autophagic flux. Consequently, cotreatment with an antioxidant but not with a pan-caspase inhibitor significantly blocked 6-OHDA-stimulated dysregulated autophagy. These results indicated that 6-OHDA-induced generation of reactive oxygen species (ROS) played a critical role in triggering neuronal death by causing dysregulated autophagy and subsequent caspase-dependent apoptosis. The results of the MTT reduction, caspase-3 activation, and TUNEL assays indicated that pharmacological inhibition of autophagy using 3-methyladenine or deletion of the autophagy-related gene Atg5 significantly inhibited 6-OHDA-induced cell death. Taken together, our results suggest that abnormal induction of autophagic flux promotes apoptotic neuronal cell death, and that the treatments limiting dysregulated autophagy may have a strong neuroprotective potential.

/pdf/dysregulated-autophagy-contributes-to-caspase-dependent-5f1pgwzr1f.pdf

Dysregulated autophagy contributes to caspase-dependent neuronal apoptosis

A review of polysaccharides from Schisandra chinensis and Schisandra sphenanthera: Properties, functions and applications

6-Hydroxydopamine induces autophagic flux dysfunction by impairing transcription factor EB activation and lysosomal function in dopaminergic neurons and SH-SY5Y cells.

Fei Liu

Papers

A review of polysaccharides from Schisandra chinensis and Schisandra sphenanthera: Properties, functions and applications

6-Hydroxydopamine induces autophagic flux dysfunction by impairing transcription factor EB activation and lysosomal function in dopaminergic neurons and SH-SY5Y cells.