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Neuromolecular Medicine

Shubhrajit Roy, Prosenjit Pal, Sampurna Ghosh, Sreyashi Bhattacharya, Shyamal Kumar Das, Prasanta Kumar Gangopadhyay, Ashish Bavdekar, Kunal Ray, Mainak Sengupta, Jharna Ray
Wilson's disease (WD), an inborn error of copper metabolism caused by mutations in the ATPase copper transporting beta (ATP7B) gene, manifests variable age of onset and different degrees of hepatic and neurological disturbances. This complex phenotypical outcome of a classical monogenic disease can possibly be explained by modifier loci regulating the clinical course of the disease. The brain-derived neurotropic factor (BDNF), critical for the survival, morphogenesis, and plasticity of the neurons, and the dopamine receptor D2 (DRD2), one of the most abundant dopamine receptors in the brain, have been highlighted in the pathophysiology of various neuropsychiatric diseases...
July 10, 2018: Neuromolecular Medicine
Hossein Sanjari Moghaddam, Zahra Valitabar, Amir Ashraf-Ganjouei, Mahtab Mojtahed Zadeh, Farzaneh Ghazi Sherbaf, Mohammad Hadi Aarabi
Parkinson' disease (PD) is characterized by motor symptoms including bradykinesia, resting tremor, postural instability, and rigidity and non-motor symptoms such as cognitive impairment, sleep disorder, and depression. Neuroinflammation has been recently implicated in pathophysiology of both motor and non-motor symptoms of PD. One of the most notable inflammatory proteins is C-reactive protein (CRP), which is elevated in the conditions of systemic inflammation. Using BioFIND database, we scrutinized the possible association between cerebrospinal fluid (CSF) levels of CRP and severity of PD motor and non-motor symptoms...
July 6, 2018: Neuromolecular Medicine
Muaz Belviranlı, Nilsel Okudan
This study aimed to determine the effect of exercise training on cognitive functioning, and hippocampal PGC-1α, FNDC5, BDNF, and other cognition-related gene and protein expression in rats. Rats were divided into 4 groups based on age [3 months (young) vs. 20 months (aged)] and training status (control vs. exercise training). The rats that exercised voluntarily performed exercise training for 90 days, and then all the rats underwent several methods of behavioral assessment. Locomotor activity and spatial memory were lower but anxiety scores were higher in the aged control rats, than in the young control, young exercised, and aged exercised rats (P < 0...
July 3, 2018: Neuromolecular Medicine
Duygu Gezen-Ak, İrem L Atasoy, Esin Candaş, Merve Alaylıoğlu, Erdinç Dursun
Our previous study demonstrated the translocation of Aβ1-42 to the nucleus in response to antibiotic treatment, and interpreted it as a possible transcriptional response of Aβ1-42 to antibiotics. The present study aims to investigate how amyloid acts on the key elements of neurodegeneration and the molecules involved in the induction of Aβ1-42 production. For this purpose, we investigated the acute effect of Aβ1-42 on the transcriptional levels of genes that have roles in the mechanisms that produce Aβ itself: alpha secretase (ADAM10), beta secretase (BACE1), the gamma secretase complex (PS-1, PS-2, Nicastrin), the substrate APP, APOE (the significant risk factor for sporadic form of the AD), TREM2 (recently indicated as a contributor to AD risk), NMDAR subunits and PKCzeta (contributors of memory and learning), and key elements of tau pathology such as tau, GSK3α, GSK3β, and Cdk5...
June 12, 2018: Neuromolecular Medicine
María Belén Ruiz-Roso, Elena Olivares-Álvaro, José Carlos Quintela, Sandra Ballesteros, Juan F Espinosa-Parrilla, Baltasar Ruiz-Roso, Vicente Lahera, Natalia de Las Heras, Beatriz Martín-Fernández
Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 (ω-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA could be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditions in BV-2 activated microglial cells...
May 30, 2018: Neuromolecular Medicine
Muskan Gupta, Gurcharan Kaur
Reactive gliosis, microgliosis, and subsequent secretion of various inflammatory mediators like cytokines, proteases, reactive oxygen, and nitrogen species are the suggested key players associated with systemic inflammation-driven neuroinflammation and cognitive impairments in various neurological disorders. Conventionally, non-steroidal anti-inflammatory drugs are prescribed to suppress inflammation but due to their adverse effects, their usage is not well accepted. Natural products are emerging better therapeutic agents due to their affordability and inherent pleiotropic biological activities...
May 30, 2018: Neuromolecular Medicine
Sun Mi Gu, Hee Pom Lee, Young Wan Ham, Dong Ju Son, Hoi Yeong Kim, Ki Wan Oh, Sang-Bae Han, Jaesuk Yun, Jin Tae Hong
Amyloidogenesis is known to cause Alzheimer's disease. Our previous studies have found that lipopolysaccharide (LPS) causes neuroinflammation and amyloidogenesis through activation of nuclear factor kappaB (NF-κB). Piperlongumine (PL) is an alkaloid amide found naturally in long pepper (Piper longum) isolates; it was reported to have inhibitory effects on NF-κB activity. We therefore investigated whether PL exhibits anti-inflammatory and anti-amyloidogenic effects by inhibiting NF-κB. A murine model of LPS-induced memory impairment was made via the intraperitoneal (i...
May 25, 2018: Neuromolecular Medicine
Anna Gójska-Grymajło, Maciej Zieliński, Dariusz Gąsecki, Kamil Kowalczyk, Mariusz Kwarciany, Barbara Seroczyńska, Walenty M Nyka
Ischemic stroke causes mobilization of various groups of progenitor cells from bone marrow to bloodstream and this correlates with the neurological status of stroke patients. The goal of our study was to identify the activity of chosen progenitor/stem cells in the peripheral blood of acute ischemic stroke patients in the first 7 days after the incident, through associations between the levels of the cells and clinical features of the patients. Thirty-three acute ischemic stroke patients and 15 non-stroke control subjects had their venous blood collected repeatedly in order to assess the levels of the CD45-CD34 + CD271+, the CD45-CD34 + CXCR4+, the CD45-CD34 + CXCR7+, and the CD45-CD34 + CD133+ stem/progenitor cells by means of flow cytometry...
May 9, 2018: Neuromolecular Medicine
Milad Hasanpour, Alireza Nourazarian, Mohammad Hossein Geranmayeh, Masoud Nikanfar, Fatemeh Khaki-Khatibi, Reza Rahbarghazi
Alzheimer's disease (AD) is commonly diagnosed by vast extracellular amyloid deposits and existence of intracellular neurofibrillary tangles. In accordance with the literature, age-related loss of sex steroid hormones in either males or females was found in relation to AD subjects. The dynamics of these hormones have been previously described in both physiological and pathological conditions with the evidence of changes in various intracellular signalings regarding the neurodegenerative disease. The potent protective effects of sex steroid hormones and their synthetic analogs are indicative of the decrease in the accumulated levels of intercellular beta-amyloid (Aβ) protein and an increase of specific proteases activity, resulting in the improvement of pathological features...
May 4, 2018: Neuromolecular Medicine
Lian Gu, Jingyan Huang, Jinhong Li, Siyun Huang, Minhua Li, Lin Gong, Tongshun Li, Li Su
A quantitative transcriptomics analysis has reported that Calmodulin 1 (CALM1) is highly expressed in human brain tissues. This study aims to evaluate the relationship between CALM1 rs3179089 polymorphism and ischemic stroke (IS) in Chinese Han population. A total of 550 patients with IS and 550 control subjects were recruited and genotyped using Sequenom MassArray technology. The mRNA expression of CALM1 was measured using quantitative real-time polymerase chain reaction. CALM1 mRNA expression was significantly higher in patients with IS than that in control subjects (P = 0...
June 2018: Neuromolecular Medicine
Le Wei, Li-Yuan Kan, Hai-Ying Zeng, Yi-Yun Tang, Hong-Lin Huang, Ming Xie, Wei Zou, Chun-Yan Wang, Ping Zhang, Xiao-Qing Tang
Our previous works have shown that hydrogen sulfide (H2 S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H2 S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H2 S by blocking hippocampal ER stress...
June 2018: Neuromolecular Medicine
Jong-Suep Baek, Jie Kai Tee, Yi Yun Pang, Ern Yu Tan, Kah Leong Lim, Han Kiat Ho, Say Chye Joachim Loo
Oral administration of levodopa (LD) is the gold standard in managing Parkinson's disease (PD). Although LD is the most effective drug in treating PD, chronic administration of LD induces levodopa-induced dyskinesia. A continuous and sustained provision of LD to the brain could, therefore, reduce peak-dose dyskinesia. In commercial oral formulations, LD is co-administrated with an AADC inhibitor (carbidopa) and a COMT inhibitor (entacapone) to enhance its bioavailability. Nevertheless, patients are known to take up to five tablets a day because of poor sustained-releasing capabilities that lead to fluctuations in plasma concentrations...
June 2018: Neuromolecular Medicine
Paulo José Lorenzoni, Rosana Herminia Scola, Claudia Suemi Kamoi Kay, Lineu Cesar Werneck, Rita Horvath, Hanns Lochmüller
Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular transmission is compromised. CMS resembling the Lambert-Eaton myasthenic syndrome (CMS-LEMS) are emerging as a rare group of distinct presynaptic CMS that share the same electrophysiological features. They have low compound muscular action potential amplitude that increment after brief exercise (facilitation) or high-frequency repetitive nerve stimulation. Although clinical signs similar to LEMS can be present, the main hallmark is the electrophysiological findings, which are identical to autoimmune LEMS...
June 2018: Neuromolecular Medicine
Kshama Ohja, Evelyne Gozal, Margaret Fahnestock, Lu Cai, Jun Cai, Jonathan H Freedman, Andy Switala, Ayman El-Baz, Gregory Neal Barnes
Autism spectrum disorders (ASD) are the most prevalent set of pediatric neurobiological disorders. The etiology of ASD has both genetic and environmental components including possible dysfunction of the immune system. The relationship of the immune system to aberrant neural circuitry output in the form of altered behaviors and communication characterized by ASD is unknown. Dysregulation of neurotrophins such as BDNF and their signaling pathways have been implicated in ASD. While abnormal cortical formation and autistic behaviors in mouse models of immune activation have been described, no one theory has been described to link activation of the immune system to specific brain signaling pathways aberrant in ASD...
June 2018: Neuromolecular Medicine
A Srivastava, S Singh, C S Rajpurohit, P Srivastava, A Pandey, D Kumar, V K Khanna, A B Pant
A perturbed cellular homeostasis is a key factor associated with xenobiotic exposure resulting in various ailments. The local cellular microenvironment enriched with secretory components aids in cell-cell communication that restores this homeostasis. Deciphering the underlying mechanism behind this restorative potential of secretome could serve as a possible solution to many health hazards. We, therefore, explored the protective efficacy of the secretome of differentiated PC12 cells with emphasis on induction of autophagy and mitochondrial biogenesis...
June 2018: Neuromolecular Medicine
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Entropy production rate is increased by several metabolic and thermodynamics abnormalities in neurodegenerative diseases (NDs). Irreversible processes are quantified by changes in the entropy production rate. This review is focused on the opposing interactions observed in NDs between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In amyotrophic lateral sclerosis and Huntington's disease, WNT/beta-catenin pathway is upregulated, whereas PPAR gamma is downregulated...
June 2018: Neuromolecular Medicine
Zusen Ye, Hao Zhang, Lingli Sun, Huan Cai, Yonggang Hao, Zongliang Xu, Zhizhong Zhang, Xinfeng Liu
Elevated C-reactive protein (CRP) levels increase the risk of poor functional disability in patients with ischemic stroke (IS). This study aimed to investigate the association between CRP gene polymorphisms and 3-month functional disability of large artery atherosclerotic (LAA) stroke in Han Chinese. Patients with first-ever LAA IS were prospectively enrolled in Nanjing Stroke Registry Program between August 2013 and October 2015. Five single-nucleotide polymorphisms (SNPs) (rs876537, rs2794520, rs3093059, rs7553007 and rs11265260) in CRP gene related to CRP levels in Asian by genome-wide association study were genotyped...
June 2018: Neuromolecular Medicine
Megan A Evans, Hyun Ah Kim, Yeong Hann Ling, Sandy Uong, Antony Vinh, T Michael De Silva, Thiruma V Arumugam, Andrew N Clarkson, Graeme R Zosky, Grant R Drummond, Brad R S Broughton, Christopher G Sobey
Acute inflammation can exacerbate brain injury after ischemic stroke. Beyond its well-characterized role in calcium metabolism, it is becoming increasingly appreciated that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-VitD3 ), has potent immunomodulatory properties. Here, we aimed to determine whether 1,25-VitD3 supplementation could reduce subsequent brain injury and associated inflammation after ischemic stroke. Male C57Bl6 mice were randomly assigned to be administered either 1,25-VitD3 (100 ng/kg/day) or vehicle i...
March 2018: Neuromolecular Medicine
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Mohammad Z Alzahrani, Saleh A Bakheet, Sabry M Attia
Autism is a neurodevelopmental disorder characterized by deficits in qualitative impairments in communication, repetitive and social interaction, restricted, and stereotyped patterns of behavior. Resveratrol has been extensively studied pharmacologically and biologically and has anti-inflammatory, antioxidant, and neuroprotective effects on neuronal damage in neurodegenerative disorders. The BTBR T+ Itpr3tf /J (BTBR) autistic mouse model has been explored for treatment of autism, which shows low reciprocal social interactions, impaired juvenile play, and decreased social approach...
March 2018: Neuromolecular Medicine
Elizabeth S Chan, Christopher Chen, Tuck Wah Soong, Boon-Seng Wong
Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), where inheritance of this isoform predisposes development of AD in a gene dose-dependent manner. Although the mode of action of ApoE4 on AD onset and progression remains unknown, we have previously shown that ApoE4, and not ApoE3 expression, resulted in insulin signaling deficits in the presence of amyloid beta (Aβ). However, these reports were not conducted with clinical samples that more accurately reflect human disease...
March 2018: Neuromolecular Medicine
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