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Neuromolecular Medicine

Shengquan Hu, Liang Wang, Shinghung Mak, Zaijun Zhang, Daping Xu, Haitao Li, Yide Li, Yuanjia Hu, Simon Ming Yuen Lee, Yuqiang Wang, Yifan Han
Danshensu (DSS) and tetramethylpyrazine (TMP) are active ingredients of Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort that are widely used in oriental medicine. Structural combination of compounds with known biological activity may lead to the formation of a molecule with multiple properties or new function profile. In the current study, the neuroprotective effects of DT-010, a novel analogue in which TMP was coupled to DSS through an ester bond and two allyl groups at the carboxyl group, were evaluated in a cellular model of Parkinson's disease (PD)...
December 2016: Neuromolecular Medicine
Rima Obeid, Ulrich Hübner, Marion Bodis, Juergen Geisel
Gene methylation is an age-related dynamic process that influences diseases. Premature aging and disturbed methylation are components of Down syndrome (DS). We studied blood biomarkers and DNA methylation (DNAm) of three CpG sites (ASPA, ITGA2B, and PDE4C) in 60 elderly subjects (mean age = 68 years), 31 subjects with DS (12.1 years) and 44 controls (12.8 years). Plasma concentrations of amyloid beta (Aβ) 1-42 and biomarkers of methylation were measured in the young groups. Subjects with DS had significantly higher concentrations of plasma S-adenosylhomocysteine (SAH) and Aβ and reduced S-adenosylmethionine/SAH ratio compared with the controls...
December 2016: Neuromolecular Medicine
Ronald S Petralia, Ya-Xian Wang, Mark P Mattson, Pamela J Yao
Here we examine the structure of the various types of spine synapses throughout the animal kingdom. Based on available evidence, we suggest that there are two major categories of spine synapses: invaginating and non-invaginating, with distributions that vary among different groups of animals. In the simplest living animals with definitive nerve cells and synapses, the cnidarians and ctenophores, most chemical synapses do not form spine synapses. But some cnidarians have invaginating spine synapses, especially in photoreceptor terminals of motile cnidarians with highly complex visual organs, and also in some mainly sessile cnidarians with rapid prey capture reflexes...
December 2016: Neuromolecular Medicine
Jing Jin, Hao Gu, Nicole M Anders, Tianhua Ren, Mali Jiang, Michael Tao, Qi Peng, Michelle A Rudek, Wenzhen Duan
Huntington's disease (HD) is a devastating neurodegenerative disease caused by the pathological elongation of the CAG repeats in the huntingtin gene. Caloric restriction (CR) has been the most reproducible environmental intervention to improve health and prolong life span. We have demonstrated that CR delayed onset and slowed disease progression in a mouse model of HD. Metformin, an antidiabetic drug, mimics CR by acting on cell metabolism at multiple levels. Long-term administration of metformin improved health and life span in mice...
December 2016: Neuromolecular Medicine
Qi Ma, Nana Liu, Ruyou Zhang, Xiaoying Li, Hui Zhang, Zongmin Li, Shuang Zhang, Wenying Hou, Qianhui Zhu, Hewei Zheng, Litao Sun
Ischemic stroke is a common neurological disease and a leading cause of permanent disability in many countries. Recent studies provide evidence on the role of the suppressor of the cytokine signaling 1 (SOCS1) gene in the development and progression of atherosclerotic lesions. However, few studies have assessed the association between single nucleotide polymorphisms (SNPs) on SOCS1 gene and ischemic stroke. Therefore, the present study aimed to investigate the role of SOCS1 polymorphism in ischemic stroke risk in a northern Chinese Han population...
December 2016: Neuromolecular Medicine
Hwa Jeong You, Jae Hyon Park, Helios Pareja-Galeano, Alejandro Lucia, Jae Il Shin
Neurodegenerative diseases are becoming an ever-increasing problem in aging populations. Low levels of brain-derived neurotrophic factor (BDNF) have previously been associated with the pathogenesis of numerous neurodegenerative diseases. Recently, microRNAs (miRNAs) have been proposed as potential novel therapeutic targets for treating various diseases of the central nervous system (CNS), and interestingly, few studies have reported several miRNAs that downregulate the expression levels of BDNF. However, substantial challenges exist when attempting to translate these findings into practical anti-miRNA therapeutics, especially when the targets remain inside the CNS...
December 2016: Neuromolecular Medicine
Michele Benigni, Claudia Ricci, Ashley R Jones, Fabio Giannini, Ammar Al-Chalabi, Stefania Battistini
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder. Since no diagnostic laboratory test exists, the identification of specific biomarkers could be fundamental in clinical practice. microRNAs (miRNAs) are considered promising biomarkers for neurodegenerative diseases. The aim of the study was to identify a CSF miRNA set that could differentiate ALS from non-ALS condition. miRNA profiling in CSF from ALS patients (n = 24; eight with C9orf72 expansion) and unaffected control subjects (n = 24) by quantitative reverse transcription PCR identified fourteen deregulated miRNAs...
December 2016: Neuromolecular Medicine
Diana Carranza, Ana Karina Vega, Sara Torres-Rusillo, Enrique Montero, Luis Javier Martinez, Manuel Santamaría, Juan Luis Santos, Ignacio J Molina
Ataxia-telangiectasia is a multisystemic disease with severe neurological affectation, immunodeficiency and telangiectasia. The disorder is caused by alterations in the ATM gene, whose size and complexity make molecular diagnosis difficult. We designed a target-enrichment next-generation sequencing strategy to characterize 28 patients from several regions of Spain. This approach allowed us to identify gene variants affecting function in 54 out of the 56 alleles analyzed, although the two unresolved alleles belong to brothers...
September 23, 2016: Neuromolecular Medicine
Pashtun Shahim, Kaj Blennow, Per Johansson, Johan Svensson, Simone Lista, Harald Hampel, Leif Christer Andersson, Henrik Zetterberg
Stanniocalcin-1 (STC-1) is a nerve cell-enriched protein involved in intracellular calcium homeostasis regulation. Changes in calcium regulation are hypothesized to play a role in the pathophysiology of Alzheimer's disease (AD). The expression of STC-1 increases in response to ischemic stroke, but whether it is altered in neurodegenerative disorder, particularly Alzheimer's disease (AD), has not been investigated before. We measured STC-1 in cerebrospinal fluid (CSF) samples from a total of 163 individuals including AD, prodromal AD (pAD), mixed AD, stable mild cognitive impairment (sMCI), and diagnoses of other dementia than AD, as well as cognitively normal controls (CNC) enrolled at academic centers in France and Sweden...
September 19, 2016: Neuromolecular Medicine
Monika Buraczynska, Kinga Buraczynska, Michal Dragan, Andrzej Ksiazek
Glutathione peroxidase 1 (Gpx1) is an endogenous antioxidant enzyme. The T allele of the Pro198Leu polymorphism in the Gpx1 (rs1050450, 198C > T) gene is associated with reduced enzyme activity. The aim of this study was to evaluate the association between Pro198Leu polymorphism and risk of diabetic peripheral neuropathy (DPN). We examined 1244 T2DM patients and 730 healthy controls. In the patient group, 33 % had diabetic peripheral neuropathy. All subjects were genotyped for the Gpx1 Pro198Leu polymorphism by polymerase chain reaction and restriction analysis...
September 3, 2016: Neuromolecular Medicine
Wei-Yi Ong, Grace Y Sun, W Gibson Wood, Teng-Nan Lin
No abstract text is available yet for this article.
September 2016: Neuromolecular Medicine
Parakalan Rangarajan, Aparna Karthikeyan, S T Dheen
Chronic neuroinflammation is a pathological feature of a number of central nervous system (CNS) diseases and is mediated by sustained activation of microglial cells, the innate immune cells of the CNS. Studies have mainly focused on identifying the molecular and epigenetic mechanisms of microglial activation. This is crucial in designing therapeutic strategies for neuropathologies in which prolonged microglial activation is known to exacerbate disease condition. In recent years, increasing evidence show that naturally occurring compounds present in regular diet could function as "nutraceuticals," arresting microglial activation, and thus conferring neuroprotection...
September 2016: Neuromolecular Medicine
Heike Asseburg, Carmina Schäfer, Madeleine Müller, Stephanie Hagl, Maximilian Pohland, Dirk Berressem, Marta Borchiellini, Christina Plank, Gunter P Eckert
Dementia contributes substantially to the burden of disability experienced at old age, and mitochondrial dysfunction (MD) was identified as common final pathway in brain aging and Alzheimer's disease. Due to its early appearance, MD is a promising target for nutritional prevention strategies and polyphenols as potential neurohormetic inducers may be strong neuroprotective candidates. This study aimed to investigate the effects of a polyphenol-rich grape skin extract (PGE) on age-related dysfunctions of brain mitochondria, memory, life span and potential hormetic pathways in C57BL/6J mice...
September 2016: Neuromolecular Medicine
Supin Chompoopong, Sunit Jarungjitaree, Tideeporn Punbanlaem, Thanaporn Rungruang, Sukumal Chongthammakun, Aikkarach Kettawan, Thongchai Taechowisan
The effects of germinated brown rice (GBR) on the motor deficits and the dopaminergic (DA) cell death were investigated in Parkinson's-like disease (PD) rats. Reactive oxidative species generated by chronic subcutaneous injection of rotenone (RT) lead to neuronal apoptosis particularly in the nigrostriatal DA system and produce many features of PD, bradykinesis, postural instability and rigidity. In this study, 4-phenylbutyric acid (4-PBA), previously reported to inhibit RT-induced DA cell death, was used as the positive control...
September 2016: Neuromolecular Medicine
Mitchell K P Lai, Wee Siong Chew, Federico Torta, Angad Rao, Greg L Harris, Jerold Chun, Deron R Herr
Sphingolipids (SPs) comprise a highly diverse class of lipids that serve biological roles both as structural components of cell membranes and as mediators of cell signaling. Pharmacologic and genetic manipulation of SPs and their signaling systems have underscored their importance in most biological processes, including central nervous system development and function. Likewise, perturbations of SP accumulation or signaling have been associated with a number of disease states, such as neural tube defects, neuroinflammation, stroke, and dementia...
September 2016: Neuromolecular Medicine
Eunice W M Chin, Guillaume Marcy, Su-In Yoon, Dongliang Ma, Francisco J Rosales, George J Augustine, Eyleen L K Goh
Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene account for approximately 95 % of all RTT cases. To model RTT in vitro, we generated induced pluripotent stem cells (iPSCs) from fibroblasts of two RTT patients with different mutations (MECP2 (R306C) and MECP2 (1155Δ32)) in their MECP2 gene. We found that these iPSCs were capable of differentiating into functional neurons. Compared to control neurons, the RTT iPSC-derived cells had reduced soma size and a decreased amount of synaptic input, evident both as fewer Synapsin 1-positive puncta and a lower frequency of spontaneous excitatory postsynaptic currents...
September 2016: Neuromolecular Medicine
Stephanie Hagl, Heike Asseburg, Martina Heinrich, Nadine Sus, Eva-Maria Blumrich, Ralf Dringen, Jan Frank, Gunter P Eckert
Aging represents a major risk factor for the development of neurodegenerative diseases like Alzheimer's disease (AD). As mitochondrial dysfunction plays an important role in brain aging and occurs early in the development of AD, the prevention of mitochondrial dysfunction might help to slow brain aging and the development of neurodegenerative diseases. Rice bran extract (RBE) contains high concentrations of vitamin E congeners and γ-oryzanol. We have previously shown that RBE increased mitochondrial function and protected from mitochondrial dysfunction in vitro and in short-term in vivo feeding studies...
September 2016: Neuromolecular Medicine
Libby Ward, Giulio Maria Pasinetti
Extensive evidence has demonstrated that psychological stress has detrimental effects on psychological health, cognitive function, and ultimately well-being. While stressful events are a significant cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The mechanisms underlying such resilience are poorly understood, and there is an urgent need to identify and target these mechanisms to promote resilience under stressful events. Botanicals have been used throughout history to treat various medical conditions; however, the development of botanical compounds into potential preventative and therapeutic agents in studies promoting brain health is hindered by the fact that most orally consumed botanicals are extensively metabolized during absorption and/or by post-absorptive xenobiotic metabolism...
September 2016: Neuromolecular Medicine
Dennis Y Chuang, Agnes Simonyi, Jiankun Cui, Dennis B Lubahn, Zezong Gu, Grace Y Sun
Microglia play a significant role in the generation and propagation of oxidative/nitrosative stress, and are the basis of neuroinflammatory responses in the central nervous system. Upon stimulation by endotoxins such as lipopolysaccharides (LPS), these cells release pro-inflammatory factors which can exert harmful effects on surrounding neurons, leading to secondary neuronal damage and cell death. Our previous studies demonstrated the effects of botanical polyphenols to mitigate inflammatory responses induced by LPS, and highlighted an important role for cytosolic phospholipase A2 (cPLA2) upstream of the pro-inflammatory pathways (Chuang et al...
September 2016: Neuromolecular Medicine
Charlene Siew-Hon Tan, Christabel Fung-Yih Ho, Swan-Ser Heng, Jui-Sheng Wu, Benny Kwong-Huat Tan, Yee-Kong Ng, Grace Y Sun, Teng-Nan Lin, Wei-Yi Ong
Clinacanthus nutans Lindau (C. nutans), commonly known as Sabah Snake Grass in southeast Asia, is widely used in folk medicine due to its analgesic, antiviral, and anti-inflammatory properties. Our recent study provided evidence for the regulation of cytosolic phospholipase A2 (cPLA2) mRNA expression by epigenetic factors (Tan et al. in Mol Neurobiol. doi: 10.1007/s12035-015-9314-z , 2015). This enzyme catalyzes the release of arachidonic acid from glycerophospholipids, and formation of pro-inflammatory eicosanoids or toxic lipid peroxidation products such as 4-hydroxynonenal...
September 2016: Neuromolecular Medicine
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