pubmed: alzheimer's and stem...
NCBI: db=pubmed; Term=alzheimer's and stem cell therapy
NCBI pubmed
  • Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer's Disease.
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    Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer's Disease.

    Mol Cells. 2015 Sep;38(9):796-805

    Authors: Kim HJ, Shin EJ, Lee BH, Choi SH, Jung SW, Cho IH, Hwang SH, Kim JY, Han JS, Chung C, Jang CG, Rhim H, Kim HC, Nah SY

    Abstract
    Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer's disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using wild-type and AD animal models. Gintonin induced [Ca(2+)]i transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated [Ca(2+)]i transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin-enriched fraction (25, 50, or 100 mg/kg, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 2 weeks) also significantly attenuated amyloid-β protein (Aβ)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltransferase (ChAT) activity and immunoreactivity, and increased acetylcholine esterase (AChE) activity. In a transgenic AD mouse model, long-term oral administration of gintonin (25 or 50 mg/kg, 3 months) also attenuated AD-related cholinergic impairments. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to Aβ and could be utilized for AD prevention or therapy.

    PMID: 26255830 [PubMed - indexed for MEDLINE]

pubmed: alzheimer's and stem...
NCBI: db=pubmed; Term=alzheimer's and stem cell treatment
NCBI pubmed
  • Nurr1 and PPARγ protect PC12 cells against MPP(+) toxicity: involvement of selective genes, anti-inflammatory, ROS generation, and antimitochondrial impairment.
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    Nurr1 and PPARγ protect PC12 cells against MPP(+) toxicity: involvement of selective genes, anti-inflammatory, ROS generation, and antimitochondrial impairment.

    Mol Cell Biochem. 2016 Jul 19;

    Authors: Jodeiri Farshbaf M, Forouzanfar M, Ghaedi K, Kiani-Esfahani A, Peymani M, Shoaraye Nejati A, Izadi T, Karbalaie K, Noorbakhshnia M, Rahgozar S, Baharvand H, Nasr-Esfahani MH

    Abstract
    Parkinson's disease (PD) can degenerate dopaminergic (DA) neurons in midbrain, substantia-nigra pars compacta. Alleviation of its symptoms and protection of normal neurons against degeneration are the main aspects of researches to establish novel therapeutic strategies. PPARγ as a member of PPARs have shown neuroprotection in a number of neurodegenerative disorders such as Alzheimer's disease and PD. Nuclear receptor related 1 protein (Nurr1) is, respectively, member of NR4A family and has received great attentions as potential target for development, maintenance, and survival of DA neurons. Based on neuroprotective effects of PPARγ and dual role of Nurr1 in anti-inflammatory pathways and development of DA neurons, we hypothesize that PPARγ and Nurr1 agonists alone and in combined form can be targets for neuroprotective therapeutic development for PD in vitro model. 1-Methyl-4-phenylpyridinium (MPP(+)) induced neurotoxicity in PC12 cells as an in vitro model for PD studies. Treatment/cotreatment with PPARγ and Nurr1 agonists 24 h prior to MPP(+) induction enhanced the viability of PC12 cell. The viability of PC12 cells was determined by MTS test. Mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were detected by flow cytometry. In addition, the relative expression of four genes including TH (the marker of DA neurons), Ephrin A1, Nurr1, and Ferritin light chain were assessed by RT-qPCR. In the MPP(+)-pretreated PC12 cells, PPARγ and Nurr1 agonists and their combined form resulted in a decrease in the cell death rate. Moreover, production of intracellular ROS and MMP modulated by MPP(+) was decreased by PPARγ and Nurr1 agonists' treatment alone and in the combined form.

    PMID: 27435855 [PubMed - as supplied by publisher]