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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...
October 10, 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)...
October 1, 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...
September 26, 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...
September 21, 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...
September 19, 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...
September 18, 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
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...
September 4, 2018: Neuromolecular Medicine
Liya Sun, Lei Xia, Mingtai Wang, Dengna Zhu, Yangong Wang, Dan Bi, Juan Song, Caiyun Ma, Chao Gao, Xiaoli Zhang, Yanyan Sun, Xiaoyang Wang, Changlian Zhu, Qinghe Xing
Cerebral palsy (CP) is a leading cause of neurological disability among young children. Congenial and adverse perinatal clinical conditions, such as genetic factors, perinatal infection, and asphyxia, are risk factors for CP. Oligodendrocyte transcription factor (OLIG2) is a protein that is expressed in brain oligodendrocyte cells and is involved in neuron repair after brain injury. In this study, we employed a Chinese Han cohort of 763 CP infants and 738 healthy controls to study the association of OLIG2 gene polymorphisms with CP...
September 3, 2018: Neuromolecular Medicine
D Khatri, D Zizioli, A Trivedi, G Borsani, E Monti, D Finazzi
Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a genetic and early-onset neurodegenerative disorder characterized by iron accumulation in the basal ganglia. It is due to mutations in Pantothenate Kinase 2 (PANK2), an enzyme that catalyzes the phosphorylation of vitamin B5, first and essential step in coenzyme A (CoA) biosynthesis. Most likely, an unbalance of the neuronal levels of this important cofactor represents the initial trigger of the neurodegenerative process, yet a complete understanding of the connection between PANK2 malfunctioning and neuronal death is lacking...
August 23, 2018: Neuromolecular Medicine
Menizibeya O Welcome, Nikos E Mastorakis
The astrocyte-neuron lactate shunt (ANLS) hypothesis is the most widely accepted model of brain glucose metabolism. However, over the past decades, research has shown that neuronal and astrocyte plasma membrane receptors, in particular, GLUT2, Kir6.2 subunit of the potassium ATP-channel, SGLT-3 acting as glucosensors, play a pivotal role in brain glucose metabolism. Although both ANLS hypothesis and glucosensor model substantially improved our understanding of brain glucose metabolism, the latter appears to be gaining more attention in the scientific community as the former could not account for new research data indicating that hypothalamic and brainstem neurons may not require astrocyte-derived lactate for energy...
September 2018: Neuromolecular Medicine
Léo Mietton, Nicolas Lebrun, Irina Giurgea, Alice Goldenberg, Benjamin Saintpierre, Juliette Hamroune, Alexandra Afenjar, Pierre Billuart, Thierry Bienvenu
A growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variants in KMT2A, a gene coding for histone methyltransferase, have been associated with Wiedemann-Steiner syndrome (WSS), a rare developmental disorder mainly characterized by intellectual disability (ID) and hypertrichosis. As KMT2A is known to regulate the expression of multiple target genes through methylation of lysine 4 of histone 3 (H3K4me), we sought to investigate the transcriptomic consequences of KMT2A variants involved in WSS...
September 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...
September 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...
September 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...
September 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...
September 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...
September 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...
September 2018: Neuromolecular Medicine
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