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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
Hao Zhang, Qijin Zhai, Zhizhong Zhang, Biyang Cai, Huan Cai, Shuyu Zhou, Lingli Sun, Yi Xie, Deyan Kong, Zongliang Xu, Kunxiong Yuan, Wenjie Zi, Xinfeng Liu, Gelin Xu
Recent genome-wide association study associated rs556621 on chromosome 6p21.1 with the risk of large artery atherosclerotic (LAA) stroke in Caucasians. However, subsequent replicate studies showed conflict results in different ethnicities. This study aimed to evaluate whether rs556621 was associated with LAA stroke in Chinese Han population. In this case-control study, 659 patients with LAA stroke and 650 healthy controls were enrolled. Associations between rs556621 genotypes and LAA stroke were analyzed with logistic regression model...
August 27, 2016: Neuromolecular Medicine
Esmat Fathi, Fatemeh Hedayati Katouli, Gholam Hossein Riazi, Marzieh Dehghan Shasaltaneh, Elham Parandavar, Samaneh Bayati, Ali Afrasiabi, Reza Nazari
Reelin is an extracellular glycoprotein which contributes to synaptic plasticity and function of memory in the adult brain. It has been indicated that the Reelin signaling cascade participates in Alzheimer's disease (AD). Besides the neurons, glial cells such as astrocytes also express Reelin protein. While functional loss of astrocytes has been reported to be associated with AD, dysfunction of astrocytic Reelin signaling pathway has not received much attention. Therefore, we investigated the effects of α-boswellic acid (ABA) as one of the major component of Boswellia serrata resin on primary fetal human astrocytes under a stress paradigm as a possible model for AD through study on Reelin cascade...
August 27, 2016: Neuromolecular Medicine
Pragyanshu Khare, Ashok K Datusalia, Shyam S Sharma
Diabetes is associated with behavioural and neurochemical alterations. In this manuscript, we are reporting the beneficial effects of parthenolide, an NF-κB inhibitor on behavioural and neurochemical deficits in type 2 diabetic rat model. Diabetes was induced by high-fat diet followed by low dose of streptozotocin (35 mg/kg). Elevated plus maze, open-field, MWM and passive avoidance test paradigm were used to assess behavioural and cognitive deficits. Three-week treatment of parthenolide (0.25 and 0.50 mg/kg; i...
August 23, 2016: Neuromolecular Medicine
Dong-Sheng Wang, Jing Han, Shuo Li, Ting Sun, Yan-Yan Guo, Wen-Bo Kang, Zhen Tian, Jian-Ning Zhao, Gang Liu, Shui-Bing Liu, Ming-Gao Zhao
Activation of translocator protein (18 kDa) (TSPO) plays an important role to mediate rapid anxiolytic efficacy in stress response and stress-related disorders by the production of neurosteroids. However, little is known about the ligand of TSPO on the anxiety-like and depressive behaviors and the underlying mechanisms in chronic unpredictable mild stress (UCMS) mice. In the present study, a novel ligand of TSPO, ZBD-2 [N-benzyl-N-ethyl-2-(7,8-dihydro-7-benzyl-8-oxo-2-phenyl-9H-purin-9-yl) acetamide] synthesized by our laboratory, was used to evaluate the anxiolytic and antidepressant efficacy and to elucidate the underlying mechanisms...
August 20, 2016: Neuromolecular Medicine
Tanja Emmerich, Laila Abdullah, Joseph Ojo, Benoit Mouzon, Thinh Nguyen, Gary S Laco, Gogce Crynen, James E Evans, Jon Reed, Michael Mullan, Fiona Crawford
Neurophysiological and neurological dysfunction is usually experienced for a short period of time in patients with mild traumatic brain injury (mTBI). However, around 15 % of patients exhibit symptoms months after TBI. Phospholipid (PL) changes have been observed in plasma from mTBI patients at chronic stages, suggesting a role in TBI pathology. We examined long-term plasma phospholipid profiles in a mouse model of mTBI to determine their translational value in reproducing PL changes observed in mTBI patients...
August 19, 2016: Neuromolecular Medicine
Patrícia S Guerreiro, Joana E Coelho, Inês Sousa-Lima, Paula Macedo, Luísa V Lopes, Tiago F Outeiro, Teresa F Pais
The protein α-synuclein (α-Syn) interferes with glucose and lipid uptake and also activates innate immune cells. However, it remains unclear whether α-Syn or its familial mutant forms contribute to metabolic alterations and inflammation in synucleinopathies, such as Parkinson's disease (PD). Here, we address this issue in transgenic mice for the mutant A53T human α-Syn (α-SynA53T), a mouse model of synucleinopathies. At 9.5 months of age, mice overexpressing α-SynA53T (homozygous) had a significant reduction in weight, exhibited improved locomotion and did not show major motor deficits compared with control transgenic mice (heterozygous)...
August 17, 2016: Neuromolecular Medicine
Yujian Chen, Yong Liu, Shide Lin, Shuguang Yang, Haiping Que, Shaojun Liu
Spinal cord injury and regeneration-related protein #69 (SCIRR69),also known as cAMP-responsive element-binding protein 3-like 2, belongs to the CREB/ATF family, some members of which play significant roles in ER stress. However, it is still not fully elucidated whether SCIRR69 involves in ER stress and its biochemical and functional roles during ER stress. In this study, we firstly treated fetal rat spinal cord neuron cells (SCN) and PC12 cells with ER stress activator thapsigargin (TG) or tunicamycin (TM) and then detected the expression pattern of SCIRR69 in response to ER stress at mRNA and protein levels using real-time PCR assay and immunoblotting...
August 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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