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Neuromolecular Medicine

Jiahong Sun, Jan Michelle Martin, Victoria Vanderpoel, Rachita K Sumbria
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia...
January 17, 2019: Neuromolecular Medicine
Djenifer B Kappel, Jaqueline B Schuch, Diego L Rovaris, Bruna S da Silva, Diana Müller, Vitor Breda, Stefania P Teche, Rudimar S Riesgo, Lavínia Schüler-Faccini, Luís A Rohde, Eugenio H Grevet, Claiton H D Bau
Neurodevelopmental disorders are prevalent, frequently occur in comorbidity and share substantial genetic correlation. Previous evidence has suggested a role for the ADGRL3 gene in Attention-Deficit/Hyperactivity Disorder (ADHD) susceptibility in several samples. Considering ADGRL3 functionality in central nervous system development and its previous association with neurodevelopmental disorders, we aimed to assess ADGRL3 influence in early-onset ADHD (before 7 years of age) and Autism Spectrum Disorder (ASD)...
January 16, 2019: Neuromolecular Medicine
Hareram Birla, Sachchida Nand Rai, Saumitra Sen Singh, Walia Zahra, Arun Rawat, Neeraj Tiwari, Rakesh K Singh, Abhishek Pathak, Surya Pratap Singh
Parkinson's disease (PD), a neurodegenerative central nervous system disorder, is characterised by progressive loss of nigrostriatal neurons in basal ganglia. Previous studies regarding PD have suggested the role of oxidative stress along with neuroinflammation in neurodegeneration. Accordingly, our study explore the anti-inflammatory activity of Tinospora cordifolia aqueous extract (TCAE) in 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP)-intoxicated Parkinsonian mouse model. MPTP-intoxicated mice showed significant behavioral and biochemical abnormalities which were effectively reversed by TCAE...
January 14, 2019: Neuromolecular Medicine
Gahee Bahn, Dong-Gyu Jo
The nuclear factor erythroid-derived 2-related factor 2 (NFE2L2/NRF2) is a master transcription factor that regulates oxidative stress-related genes containing the antioxidant response element (ARE) in their promoters. The damaged function and altered localization of NRF2 are found in most neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis. These neurodegenerative diseases developed from various risk factors such as accumulated oxidative stress and genetic and environmental elements...
January 7, 2019: Neuromolecular Medicine
Nihan Hande Akçakaya, Barış Salman, Zeliha Görmez, Yelda Tarkan Argüden, Ayşe Çırakoğlu, Raif Çakmur, Berril Dönmez Çolakoğlu, Seniha Hacıhanefioğlu, Uğur Özbek, Zuhal Yapıcı, Sibel Aylin Uğur İşeri
Beta-propeller protein-associated neurodegeneration (BPAN) is an X-linked rare dominant disorder of autophagy. The role of WDR45 has been implicated in BPAN almost exclusively in females possibly due to male lethality. Characterization of distinctive clinical manifestations and potentially the complex genetic determinants in rare male patients remain crucial for deciphering BPAN and other X-linked dominant diseases. We performed whole exome sequencing (WES) followed by segregation analysis and identified a novel nonsense and mosaic variant in WDR45, namely NM_007075...
January 5, 2019: Neuromolecular Medicine
Guan Sun, Ying Cao, Xueliang Dai, Min Li, Jun Guo
Heat shock cognate protein 70 (Hsc70) is a key mediator for the maintenance of intracellular proteins and regulates cellular activities. And it is elevated in various tumor tissues including glioma, which is closely related to the malignancy and poor prognosis of the tumors. However, the effects of Hsc70 on gliomas and its regulatory mechanism have not yet been elucidated. In the present study, we found that Hsc70 was overexpressed in glioma tissues and cultured glioma cells. Furthermore, Hsc70 expression exhibited positive correlation with the grades of gliomas...
January 3, 2019: Neuromolecular Medicine
Yajing Mi, Xingchun Gao, Hao Xu, Yuanyuan Cui, Yuelin Zhang, Xingchun Gou
Huntington's disease (HD) is an autosomal dominant and fatal neurodegenerative disorder, which is caused by an abnormal CAG repeat in the huntingtin gene. Despite its well-defined genetic origin, the molecular mechanisms of neuronal death are unclear yet, thus there are no effective strategies to block or postpone the process of HD. Ferroptosis, a recently identified iron-dependent cell death, attracts considerable attention due to its putative involvement in neurodegenerative diseases. Accumulative data suggest that ferroptosis is very likely to participate in HD, and inhibition of the molecules and signaling pathways involved in ferroptosis can significantly eliminate the symptoms and pathology of HD...
January 2, 2019: Neuromolecular Medicine
Vasileios Siokas, Dimitrios Kardaras, Athina-Maria Aloizou, Ioannis Asproudis, Konstadinos G Boboridis, Eleni Papageorgiou, Georgios M Hadjigeorgiou, Evangelia E Tsironi, Efthimios Dardiotis
A few genetic variants are implicated in the development of blepharospasm (BSP). The precise role of the rs6265 on the brain-derived neurotrophic factor (BDNF) gene on BSP remains controversial. The effect of rs6265 on BSP was evaluated. 206 patients with BSP and 206 healthy controls were recruited and genotyped for the rs6265. We also performed a meta-analysis, by pooling our results with those from previous studies. A significant effect of rs6265 on the risk of BSP was found in the dominant model of inheritance [odds ratio (OR) (95% confidence interval (CI) 1...
December 5, 2018: Neuromolecular Medicine
Liting Hang, John Thundyil, Geraldine W Y Goh, Kah-Leong Lim
Parkinson's disease (PD) is a prevalent neurodegenerative movement disorder that is characterized pathologically by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) of the midbrain. Despite intensive research, the etiology of PD remains poorly understood. Interestingly, recent studies have implicated neuronal energy dysregulation as one of the key perpetrators of the disease. Supporting this, we have recently demonstrated that pharmacological or genetic activation of AMP kinase (AMPK), a master regulator of cellular energy homeostasis, rescues the pathological phenotypes of Drosophila models of PD...
November 8, 2018: Neuromolecular Medicine
Liara Rizzi, Luciane Missiaggia, Matheus Roriz-Cruz
The purpose of the study was to determine whether Aβ1-42 and p-Tau181 cerebral spinal fluid (CSF) levels can predict progression from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease dementia (ADD) in a 3-year follow-up study. All participants were evaluated blindly by a behavioral neurologist and a neuropsychologist, and classified according to the Petersen criteria for aMCI and according to the Clinical Dementia Rating (CDR) scale. Individuals were also submitted to lumbar puncture at baseline...
December 2018: Neuromolecular Medicine
Anat Shmueli, Tali Shalit, Eitan Okun, Galit Shohat-Ophir
Toll receptors, first identified to regulate embryogenesis and immune responses in the adult fly and subsequently defined as the principal sensors of infection in mammals, are increasingly appreciated for their impact on the homeostasis of the central as well as the peripheral nervous systems. Whereas in the context of immunity, the fly Toll and the mammalian TLR pathways have been researched in parallel, the expression pattern and functionality have largely been researched disparately. Herein, we provide data on the expression pattern of the Toll homologues, signaling components, and downstream effectors in ten different cell populations of the adult fly central nervous system (CNS)...
December 2018: Neuromolecular Medicine
Marton Tompa, Ferenc Kalovits, Adam Nagy, Bernadette Kalman
Glioblastoma (GBM), a highly lethal brain tumor, has been comprehensively characterized at the molecular level with the identification of several potential treatment targets. Data concerning the Wnt pathway are relatively sparse, but apparently very important in defining several aspects of tumor biology. The Wnt ligands are involved in numerous basic biological processes including regulation of embryogenic development, cell fate determination, and organogenesis, but growing amount of data also support the roles of Wnt pathways in the formation of many tumors, including gliomas...
December 2018: Neuromolecular Medicine
Sung-Chun Tang, Kai-Chien Yang, Chih-Hao Chen, Shieh-Yueh Yang, Ming-Jang Chiu, Chau-Chung Wu, Jiann-Shing Jeng
Increases in plasma of β-amyloids (Aβ) and tau proteins have been noted in patients with Alzheimer's dementia (AD). Our study investigated the associations of plasma Aβ and tau proteins with dementia in stroke patients. This cross-sectional study recruited 24 controls (mean age: 67.4 ± 7.5 years, 33.3% male), 27 stroke patients without dementia (mean age: 70.7 ± 6.9 years, 60.7% male), 34 stroke patients with dementia (mean age: 78.3 ± 5.3 years, 45.5% male, Clinical Dementia Ranking (CDR): 1...
December 2018: Neuromolecular Medicine
Malavika Srikanth, Kalashobini Chandrasaharan, Xinyuan Zhao, Kanokporn Chayaburakul, Wei-Yi Ong, Deron R Herr
DHA is one of the most abundant fatty acids in the brain, largely present in stores of membrane phospholipids. It is readily released by the action of phospholipase A2 and is known to induce anti-inflammatory and neurotrophic effects. It is not thought to contribute to proinflammatory processes in the brain. In this study, an immortalized murine microglia cell line (BV-2) was used to evaluate the effect of DHA on neuroinflammatory cells. Pretreatment of BV-2 cells with low concentrations of DHA (30 µM) attenuates lipopolysaccharide-mediated inflammatory cytokine gene expression, consistent with known anti-inflammatory effects...
December 2018: Neuromolecular Medicine
Natalia Wawrusiewicz-Kurylonek, Monika Chorąży, Renata Posmyk, Olga Zajkowska, Agata Zajkowska, Adam Jacek Krętowski, Joanna Tarasiuk, Jan Kochanowicz, Alina Kułakowska
The FOXP3 gene encodes a transcription factor and is predominantly expressed in the CD4+ CD25+ regulatory T cells which plays a pivotal role in the maintenance of immune homeostasis. The defect of FOXP3 gene may provide a critical link between autoimmunity and immune deficiency. The purpose of our study was to evaluate the association of chosen polymorphisms of FOXP3 gene (rs3761549, rs3761548, rs3761547) with different clinical multiple sclerosis (MS) data of our relapsing-remitting groups of patients and in control group...
December 2018: Neuromolecular Medicine
Wanli Yu, Sai Liang, Chunzhi Zhang
GBM is the highest incidence in primary intracranial malignancy, and it remains poor prognosis even though the patient is gave standard treatment. Despite decades of intense research, the complex biology of GBM remains elusive. In view of eight hallmarks of cancer which were proposed in 2011, studies related to the eight biological capabilities in GBM have made great progress. From these studies, it can be inferred that miRs, as a mode of post-transcriptional regulation, are involved in regulating these malignant biological hallmarks of GBM...
December 2018: Neuromolecular Medicine
Mohit Kumar, Rajat Sandhir
Homocysteine (Hcy) is a sulfur-containing amino acid derived from methionine metabolism. Elevated plasma Hcy levels (> 15 µM) result in a condition called hyperhomocysteinemia (HHcy), which is an independent risk factor in the development of various neurodegenerative disorders. Reactive oxygen species (ROS) produced by auto-oxidation of Hcy have been implicated in HHcy-associated neurological conditions. Hydrogen sulfide (H2 S) is emerging as a potent neuroprotective and neuromodulator molecule. The present study was aimed to evaluate the ability of NaHS (a source of H2 S) to attenuate Hcy-induced oxidative stress and altered antioxidant status in animals subjected to HHcy...
December 2018: Neuromolecular Medicine
Weam Fageera, Sarojini M Sengupta, Aurelie Labbe, Natalie Grizenko, Ridha Joober
Results of candidate gene investigations in ADHD have been difficult to replicate. The complexity of the phenotypes and their underlying determinants, and the relatively small effect sizes of genetic variants may, in part, be contributing to these inconsistencies. The objective of this study is to conduct an exploratory analysis using a comprehensive approach to investigate the role of candidate genes. This approach combines a dimensional behavioural approach akin to Research Domain Criteria (RDoC), a pharmaco-dynamic evaluation of behaviours relevant to ADHD, together with association and linkage testing in a large sample of children with ADHD...
December 2018: Neuromolecular Medicine
Abdolkarim Hosseini, Homayoun Khazali
It is an established fact that orexin plays an important role in regulating the reproductive axis and the secretions of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH). However, its precise cellular and molecular mechanisms are not fully recognized. Accordingly, the aim of the present study is to find out whether the central injection of orexin A (OXA) and its antagonists, SB-334867 (as orexin receptor antagonist 1; OX1RA) and JNJ-10397049 (as orexin receptor antagonist 2; OX2RA), either alone or in combination, can leave any impact on the reproductive axis (either hormonal or behavioral) in the male Wistar rats...
September 14, 2018: Neuromolecular Medicine
Yueqing Gong, Kun Wang, Sheng-Ping Xiao, Panying Mi, Wanjie Li, Yu Shang, Fei Dou
Human tetratricopeptide repeat domain 3 (TTC3) is a gene on 21q22.2 within the Down syndrome critical region (DSCR). Earlier studies suggest that TTC3 may be an important regulator in individual development, especially in neural development. As an E3 ligase, TTC3 binds to phosphorylated Akt and silence its activity via proteasomal cascade. Several groups also reported the involvement of TTC3 in familial Alzheimer's disease recently. In addition, our previous work shows that TTC3 also regulates the degradation of DNA polymerase gamma and over-expressed TTC3 protein tends to form insoluble aggregates in cells...
September 10, 2018: Neuromolecular Medicine
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