Notch Inhibitors from Calotropis gigantea That Induce Neuronal Differentiation of Neural Stem Cells

Guo

Neurorehabil Neural Repair

et al. 2020

Background. Ischemic stroke carries a high mortality rate and is a leading cause of severe neurological disability. However, the efficacy of current therapeutic options remains limited. Objective. We aimed to investigate the treatment efficacy of transcranial direct current stimulation (tDCS) in motor function rehabilitation after ischemic stroke and explore the underlying mechanisms. Methods. Male Sprague-Dawley rats with epicranial electrodes were used to establish pathogenetic model through temporary right middle cerebral artery occlusion (MCAO). Subsequently, animals were randomly divided into 4 groups: MCAO + tDCS/sham tDCS, Control + tDCS/sham tDCS. Animals in the groups with tDCS underwent 10 days of cathodal tDCS totally (500 µA, 15 minutes, once a day). During and after tDCS treatment, the motor functions of the animals, ischemic damage area, proliferation and differentiation of neural stem cells (NSCs), and distribution, and protein expression of Notch1 signaling molecules were detected. Results. The rehabilitation of MCAO-induced motor function deficits was dramatically accelerated by tDCS treatment. NSC proliferation in the subventricular zone (SVZ) was significantly increased after MCAO surgery, and tDCS treatment promoted this process. Additionally, NSCs probably migrated from the SVZ to the ischemic striatum and then differentiated into neurons and oligodendrocytes after MCAO surgery, both of which processes were accelerated by tDCS treatment. Finally, tDCS treatment inhibited the activation of Notch1 signaling in NSCs in the ischemic striatum, which may be involved in NSC differentiation in the MCAO model. Conclusion. Our results suggest that tDCS may exert therapeutic efficacy after ischemic stroke in a regenerative medical perspective.

Section: Discussionmentioning

confidence: 94%

tDCS Accelerates the Rehabilitation of MCAO-Induced Motor Function Deficits via Neurogenesis Modulated by the Notch1 Signaling Pathway

Guo

Neurorehabil Neural Repair

et al. 2020

“…HES5 (targeted by miR-219) is an established factor in neuronal differentiation that becomes downregulated during this process to allow for MASH1 expression that is necessary for this process [92]. HES5 is also the target of a pre-clinical study aimed at treating AD and PD [93].…”

Section: Resultsmentioning

confidence: 99%

Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans

Brennan¹,

Keon²,

Liu³

et al. 2019

Mol Neurobiol

Neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and dementia pose one of the greatest health challenges this century. Although these NDs have been looked at as single entities, the underlying molecular mechanisms have never been collectively visualized to date. With the advent of high-throughput genomic and proteomic technologies, we now have the opportunity to visualize these diseases in a whole new perspective, which will provide a clear understanding of the primary and secondary events vital in achieving the final resolution of these diseases guiding us to new treatment strategies to possibly treat these diseases together. We created a knowledge base of all microRNAs known to be differentially expressed in various body fluids of ND patients. We then used several bioinformatic methods to understand the functional intersections and differences between AD, PD, ALS, and MS. These results provide a unique panoramic view of possible functional intersections between AD, PD, MS, and ALS at the level of microRNA and their cognate genes and pathways, along with the entities that unify and separate them. While the microRNA signatures were apparent for each ND, the unique observation in our study was that hsa-miR-30b-5p overlapped between all four NDS, and has significant functional roles described across NDs. Furthermore, our results also show the evidence of functional convergence of miRNAs which was associated with the regulation of their cognate genes represented in pathways that included fatty acid synthesis and metabolism, ECM receptor interactions, prion diseases, and several signaling pathways critical to neuron differentiation and survival, underpinning their relevance in NDs. Envisioning this group of NDs together has allowed us to propose new ways of utilizing circulating miRNAs as biomarkers and in visualizing diverse NDs more holistically . The critical molecular insights gained through the discovery of ND-associated miRNAs, overlapping miRNAs, and the functional convergence of microRNAs on vital pathways strongly implicated in neurodegenerative processes can prove immensely valuable in the identifying new generation of biomarkers, along with the development of miRNAs into therapeutics.Electronic supplementary materialThe online version of this article (10.1007/s12035-019-1615-1) contains supplementary material, which is available to authorized users.

Nat. Prod. Bioprospect.

“… Thankuni Herb Leaves Memory loss, mental disorder, insanity Alzheimer's disease, Parkinson’s disease [ 14 , 47 , 89 , 104 – 106 ] Foeniculum vulgare Mill Mouri Herb Fruit, seed Nervous debility, headache Enhances cognitive function and memory [ 107 – 109 ] Apocynaceae Alstonia scholaris (L.) R.Br. Satim Tree Bark Nervous debility (Or) anti-dopaminergic (schizophrenia) [ 88 , 110 , 111 ] Calotropis gigantea (L.) W.T.Aiton Bara akand Shrub Shoot Paralysis (Or) Alzheimer's disease and Parkinson's disease [ 91 , 111 , 112 ] Carissa carandas L. Karamcha Tree Fruit Insanity, headache Anticonvulsant [ 113 – 115 ] Hemidesmus indicus (L.) R.Br. Anantamul Shrub Leaves, root Mental disorder, nervous debility, heat stroke Anticholinesterase activity [ 113 , …”

Section: Introductionmentioning

confidence: 99%

Traditional Herbal Medicines Against CNS Disorders from Bangladesh

Uddin

Zidorn

2020

The majority of the population in Bangladesh uses traditional plant-based medicines to manage various ailments, including central nervous system (CNS) disorders. This review presents ethnobotanical information and relevant scientific studies on plants used in traditional healthcare for the management of various CNS disorders in Bangladesh. The information on the medicinal plants of Bangladesh effective against CNS disorders published in scientific journals, books, and reports was compiled from different electronic databases using specific key words. The present article provides comprehensive information on a total of 224 medicinal plant species belonging to 81 families used for the treatment of CNS disorders by the various peoples of Bangladesh. In total, we reviewed more than 290 relevant papers. In this study, leaves were found as the most often used plant organ, followed by roots, fruits, whole plants, barks, seeds, stems, rhizomes, and flowers. The Fabaceae family contributes the highest number of used species, followed by Rubiaceae, Lamiaceae, Cucurbitaceae, Vitaceae, Euphorbiaceae, Malvaceae, and Zingiberaceae. The most frequently used species (in decreasing order) are Asparagus racemosus, Centella asiatica, Stephania japonica, Aegle marmelos, Coccinia grandis, Tabernaemontana divaricata, Bacopa monnieri, Abroma augusta, and Scoparia dulcis. This review may serve as a starting point for a rational search for neuroactive natural products against CNS disorders within the Flora of Bangladesh. Graphic Abstract