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https://www.readbyqxmd.com/read/28225235/-multiple-sclerosis-a-mitochondria-mediated-disease
#1
Kristin N Varhaug, Christian A Vedeler, Charalampos Tzoulis, Laurence A Bindoff
BACKGROUND Mitochondria play an important role in the pathogenesis of various neurodegenerative disorders, including Parkinson's disease. Neurodegenerative changes occur early in the course of multiple sclerosis (MS). This article aims to present information on a possible association between mitochondrial dysfunction and multiple sclerosis.MATERIAL AND METHOD The article is based on original and review articles selected following a literature search in PubMed, restricted to articles written in English, and concluded in May 2016...
February 2017: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
https://www.readbyqxmd.com/read/28224980/alpha-synuclein-prevents-the-formation-of-spherical-mitochondria-and-apoptosis-under-oxidative-stress
#2
Stefanie Menges, Georgia Minakaki, Patrick M Schaefer, Holger Meixner, Iryna Prots, Ursula Schlötzer-Schrehardt, Kristina Friedland, Beate Winner, Tiago F Outeiro, Konstanze F Winklhofer, Christine A F von Arnim, Wei Xiang, Jürgen Winkler, Jochen Klucken
Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson's disease. Nevertheless, the role of aSyn in mitochondrial physiology remains elusive. Thus, we addressed the impact of aSyn specifically on mitochondrial response to OS in neural cells. We characterize a distinct type of mitochondrial fragmentation, following H2O2 or 6-OHDA-induced OS, defined by spherically-shaped and hyperpolarized mitochondria, termed "mitospheres"...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28222786/post-translational-modification-of-parkin
#3
REVIEW
Joy Chakraborty, Valentina Basso, Elena Ziviani
: Mutations in the gene encoding for the E3 ubiquitin ligase Parkin are associated to a rare form of familiar autosomal recessive Parkinsonism. Despite decades of research on the Parkin protein, whose structure has been recently solved, little is known about the specific signalling pathways that lead to Parkin activation. Parkin activity spans from mitochondria quality control to tumor suppression and stress protection; it is thus tempting to hypothesize that the broad impact of Parkin on cellular physiology might be the result of different post translational modifications that can be controlled by balanced opposing events...
February 21, 2017: Biology Direct
https://www.readbyqxmd.com/read/28222515/meta-analysis-of-parkinson-s-disease-and-alzheimer-s-disease-revealed-commonly-impaired-pathways-and-dysregulation-of-nrf2-dependent-genes
#4
Qian Wang, Wen-Xing Li, Shao-Xing Dai, Yi-Cheng Guo, Fei-Fei Han, Jun-Juan Zheng, Gong-Hua Li, Jing-Fei Huang
Many lines of evidence suggest that Parkinson's disease (PD) and Alzheimer's disease (AD) have common characteristics, such as mitochondrial dysfunction and oxidative stress. As the underlying molecular mechanisms are unclear, we perform a meta-analysis with 9 microarray datasets of PD studies and 7 of AD studies to explore it. Functional enrichment analysis revealed that PD and AD both showed dysfunction in the synaptic vesicle cycle, GABAergic synapses, phagosomes, oxidative phosphorylation, and TCA cycle pathways, and AD had more enriched genes...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28220655/ppars-in-the-central-nervous-system-roles-in-neurodegeneration-and-neuroinflammation
#5
Juan M Zolezzi, Manuel J Santos, Sussy Bastías-Candia, Claudio Pinto, Juan A Godoy, Nibaldo C Inestrosa
Over 25 years have passed since peroxisome proliferators-activated receptors (PPARs), were first described. Like other members of the nuclear receptors superfamily, PPARs have been defined as critical sensors and master regulators of cellular metabolism. Recognized as ligand-activated transcription factors, they are involved in lipid, glucose and amino acid metabolism, taking part in different cellular processes, including cellular differentiation and apoptosis, inflammatory modulation and attenuation of acute and chronic neurological damage in vivo and in vitro...
February 20, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28215578/mfn2-protects-dopaminergic-neurons-exposed-to-paraquat-both-in-vitro-and-in-vivo-implications-for-idiopathic-parkinson-s-disease
#6
Fanpeng Zhao, Wenzhang Wang, Chunyu Wang, Sandra L Siedlak, Hisashi Fujioka, Beisha Tang, Xiongwei Zhu
Mitochondrial dynamics and quality control plays a critical role in the maintenance of mitochondrial homeostasis and function. Pathogenic mutations of many genes associated with familial Parkinson's disease (PD) caused abnormal mitochondrial dynamics, suggesting a likely involvement of disturbed mitochondrial fission/fusion in the pathogenesis of PD. In this study, we focused on the potential role of mitochondrial fission/fusion in idiopathic PD patients and in neuronal cells and animals exposed to paraquat (PQ), a commonly used herbicide and PD-related neurotoxin, as models for idiopathic PD...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28215142/small-molecule-modulation-of-hdac6-activity-the-propitious-therapeutic-strategy-to-vanquish-neurodegenerative-disorders
#7
Shabir Ahmad Ganai
Histone deacetylases (HDACs) are epigenetic enzymes creating the transcriptionally inactive state of chromatin by erasing acetyl moiety from histone and non-histone substrates. HDAC6 modulates several biological pathways in dividing cells as well as in post-mitotic neurons, and has been implicated in the pathophysiology of neurodegeneration. The distinct cellular functions and survival in these cells are reliant on HDAC6-mediated processes including intracellular trafficking, chaperone-mediated stress responses, anti-oxidation and protein degradation...
8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28214539/lumbee-traditional-medicine-neuroprotective-activities-of-medicinal-plants-used-to-treat-parkinson-s-disease-related-symptoms
#8
Aurélie de Rus Jacquet, Michael Timmers, Sin Ying Ma, Andrew Thieme, George P McCabe, Jay Hansford C Vest, Mary Ann Lila, Jean-Christophe Rochet
ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta and the presence in surviving neurons of Lewy body inclusions enriched with aggregated forms of the presynaptic protein α-synuclein (aSyn). Although current therapies provide temporary symptomatic relief, they do not slow the underlying neurodegeneration in the midbrain. In this study, we analyzed contemporary herbal medicinal practices used by members of the Lumbee tribe to treat PD-related symptoms, in an effort to identify safe and effective herbal medicines to treat PD...
February 15, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28213158/pink1-parkin-mitophagy-and-neurodegeneration-what-do-we-really-know-in-vivo
#9
REVIEW
Alexander J Whitworth, Leo J Pallanck
Mitochondria are essential organelles that provide cellular energy and buffer cytoplasmic calcium. At the same time they produce damaging reactive oxygen species and sequester pro-apoptotic factors. Hence, eukaryotes have evolved exquisite homeostatic processes that maintain mitochondrial integrity, or ultimately remove damaged organelles. This subject has garnered intense interest recently following the discovery that two Parkinson's disease genes, PINK1 and parkin, regulate mitochondrial degradation (mitophagy)...
February 14, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28212723/redox-dynamics-of-manganese-as-a-mitochondrial-life-death-switch
#10
REVIEW
Matthew Ryan Smith, Jolyn Fernandes, Young-Mi Go, Dean P Jones
Sten Orrenius, M.D., Ph.D., pioneered many areas of cellular and molecular toxicology and made seminal contributions to our knowledge of oxidative stress and glutathione (GSH) metabolism, organellar functions and Ca(+2)-dependent mechanisms of cell death, and mechanisms of apoptosis. On the occasion of his 80(th) birthday, we summarize current knowledge on redox biology of manganese (Mn) and its role in mechanisms of cell death. Mn is found in all organisms and has critical roles in cell survival and death mechanisms by regulating Mn-containing enzymes such as manganese superoxide dismutase (SOD2) or affecting expression and activity of caspases...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28211874/datf4-regulation-of-mitochondrial-folate-mediated-one-carbon-metabolism-is-neuroprotective
#11
Ivana Celardo, Susann Lehmann, Ana C Costa, Samantha Hy Loh, L Miguel Martins
Neurons rely on mitochondria as their preferred source of energy. Mutations in PINK1 and PARKIN cause neuronal death in early-onset Parkinson's disease (PD), thought to be due to mitochondrial dysfunction. In Drosophila pink1 and parkin mutants, mitochondrial defects lead to the compensatory upregulation of the mitochondrial one-carbon cycle metabolism genes by an unknown mechanism. Here we uncover that this branch is triggered by the activating transcription factor 4 (ATF4). We show that ATF4 regulates the expression of one-carbon metabolism genes SHMT2 and NMDMC as a protective response to mitochondrial toxicity...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28210207/cannabinoid-receptor-2-signaling-in-neurodegenerative-disorders-from-pathogenesis-to-a-promising-therapeutic-target
#12
REVIEW
Tommaso Cassano, Silvio Calcagnini, Lorenzo Pace, Federico De Marco, Adele Romano, Silvana Gaetani
As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28204825/morroniside-protects-sk-n-sh-human-neuroblastoma-cells-against-h2o2-induced-damage
#13
Jing-Xing Zhang, Rui Wang, Jin Xi, Lin Shen, An-You Zhu, Qi Qi, Qi-Yi Wang, Lun-Jun Zhang, Feng-Chao Wang, He-Zuo Lü, Jian-Guo Hu
Oxidative stress-induced cell injury has been linked to the pathogenesis of neurodegenerative disorders such as spinal cord injury, Parkinson's disease, and multiple sclerosis. Morroniside is an antioxidant derived from the Chinese herb Shan-Zhu-Yu. The present study investigated the neuroprotective effect of morroniside against hydrogen peroxide (H2O2)-induced cell death in SK-N-SH human neuroblastoma cells. H2O2 increased cell apoptosis, as determined by flow cytometry and Hoechst 33342 staining. This effect was reversed by pretreatment with morroniside at concentrations of 1-100 µM...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28197854/mitochondrial-complex-i-activity-is-conditioned-by-supercomplex-i-iii2-iv-assembly-in-brain-cells-relevance-for-parkinson-s-disease
#14
Irene Lopez-Fabuel, Monica Resch-Beusher, Monica Carabias-Carrasco, Angeles Almeida, Juan P Bolaños
The assembly of complex I (CI) with complexes III (CIII) and IV (CIV) of the mitochondrial respiratory chain (MRC) to configure I-III- or I-III-IV-containing supercomplexes (SCs) regulates mitochondrial energy efficiency and reactive oxygen species (mROS) production. However, whether the occurrence of SCs impacts on CI specific activity remains unknown to our knowledge. To investigate this issue, here we determined CI activity in primary neurons and astrocytes, cultured under identical antioxidants-free medium, from two mouse strains (C57Bl/6 and CBA) and Wistar rat, i...
February 14, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28193887/tmem175-deficiency-impairs-lysosomal-and-mitochondrial-function-and-increases-%C3%AE-synuclein-aggregation
#15
Sarah Jinn, Robert E Drolet, Paige E Cramer, Andus Hon-Kit Wong, Dawn M Toolan, Cheryl A Gretzula, Bhavya Voleti, Galya Vassileva, Jyoti Disa, Marija Tadin-Strapps, David J Stone
Parkinson disease (PD) is a neurodegenerative disorder pathologically characterized by nigrostriatal dopamine neuron loss and the postmortem presence of Lewy bodies, depositions of insoluble α-synuclein, and other proteins that likely contribute to cellular toxicity and death during the disease. Genetic and biochemical studies have implicated impaired lysosomal and mitochondrial function in the pathogenesis of PD. Transmembrane protein 175 (TMEM175), the lysosomal K(+) channel, is centered under a major genome-wide association studies peak for PD, making it a potential candidate risk factor for the disease...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28192238/molecular-networks-related-to-the-immune-system-and-mitochondria-are-targets-for-the-pesticide-dieldrin-in-the-zebrafish-danio-rerio-central-nervous-system
#16
Andrew M Cowie, Kathleena I Sarty, Angella Mercer, Jin Koh, Karen A Kidd, Christopher J Martyniuk
: The objectives of this study were to determine the behavioral and molecular responses in the adult zebrafish (Danio rerio) central nervous system (CNS) following a dietary exposure to the pesticide dieldrin. Zebrafish were fed pellets spiked with 0.03, 0.15, or 1.8μg/g dieldrin for 21days. Behavioral analysis revealed no difference in exploratory behaviors or those related to anxiety. Transcriptional networks for T-cell aggregation and selection were decreased in expression suggesting an immunosuppressive effect of dieldrin, consistent with other studies investigating organochlorine pesticides...
February 9, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28187263/tetrahydroxystilbene-glucoside-inhibits-%C3%AE-synuclein-aggregation-and-apoptosis-in-a53t-%C3%AE-synuclein-transfected-cells-exposed-to-mpp-sup-sup
#17
Ruyi Zhang, Fangling Sun, Lan Zhang, Xuejing Sun, Lin Li
Increasing evidence has solidified the involvement of α-synuclein (α-Syn) and neurotoxins in the pathogenesis of Parkinson's disease (PD), suggesting a combination of genetic and environmental influences. 2,3,5,4'-Tetrahydroxystilbene -2-O-β-D-glucoside (TSG) is one of the main active components extracted from Polygonum multiflorum. The purpose of the present study was to investigate the effects of TSG on α-Syn aggregation, mitochondrial dysfunction, oxidative stress and apoptosis in vitro. A53T mutant α-synuclein-transfected cells (A53T AS cells) plus MPP+<sup></sup> exposure were used as a complex cell model of PD...
February 10, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28185818/amentoflavone-protects-dopaminergic-neurons-in-mptp-induced-parkinson-s-disease-model-mice-through-pi3k-akt-and-erk-signaling-pathways
#18
Qin Cao, Liyue Qin, Fei Huang, Xiaoshuang Wang, Liu Yang, Hailian Shi, Hui Wu, Beibei Zhang, Ziyu Chen, Xiaojun Wu
Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Mitochondrial dysfunction and cell apoptosis are suggested to be actively involved in the pathogenesis of PD. In the present study, the neuroprotective effect of amentoflavone (AF), a naturally occurring biflavonoid from Selaginella tamariscina, was examined in PD models both in vitro and in vivo. On SH-SY5Y cells, AF treatment dose-dependently reduced 1-methyl-4-phenylpyridinium (MPP(+))-induced nuclear condensation and loss of cell viability without obvious cytotoxicity...
February 6, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28178523/the-mitochondrial-rhomboid-protease-parl-is-regulated-by-pdk2-to-integrate-mitochondrial-quality-control-and-metabolism
#19
Guang Shi, G Angus McQuibban
Mitochondrial quality control (MQC) systems are essential for mitochondrial health and normal cellular function. Dysfunction of MQC is emerging as a central mechanism for the pathogenesis of various diseases, including Parkinson's disease. The mammalian mitochondrial rhomboid protease, PARL, has been proposed as a regulator of PINK1/PARKIN-mediated mitophagy, which is an essential component of MQC. PARL undergoes an N-terminal autocatalytic cleavage (β cleavage), which is required for efficient mitophagy...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28174514/associations-among-cognitive-functions-plasma-dna-and-white-matter-integrity-in-patients-with-early-onset-parkinson-s-disease
#20
Yueh-Sheng Chen, Meng-Hsiang Chen, Cheng-Hsien Lu, Pei-Chin Chen, Hsiu-Ling Chen, I-Hsiao Yang, Nai-Wen Tsai, Wei-Che Lin
Early-onset Parkinson's disease (EOPD) patients are symptomatic at a relatively young age, and the impacts of the disease on both the patients and their caregivers are dramatic. Few studies have reported on the cognitive impairments seen in EOPD, and the results of these studies have been diverse. Furthermore, it is still unclear what microstructural white matter (WM) changes are present in EOPD patients. As such, we conducted this study to investigate the microstructural WM changes experienced by EOPD patients and their association with cognitive function and plasma DNA levels...
2017: Frontiers in Neuroscience
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