Poster at the annual meeting of the European Brain and Behaviour Society (EBBS) 2013, Munich (Germany). Martin Engel, Xu-Feng Huang, Elisabeth Frank. Background: Neuregulin-1 is critical for neurodevelopment, but also found to alter acute brain signalling in adulthood. Alterations of the Neuregulin-1-ErbB4 signalling pathway are shown to be relevant for the schizophrenia pathology. ErbB4 receptors were found primarily located on GABAergic interneurons in schizophrenia-relevant brain areas, including the hippocampus. Using application of phencyclidine (PCP) both schizophrenia-like symptoms can be induced as well as GABAergic neurotransmission altered. Antagonism of PCP-induced effects was previously used as an indicator for the antipsychotic potential of a compound.. In the presented studies, we therefore explored the potential of Neuregulin-1 application to suppress PCP-induced hyperlocomotion as well as PCP-induced GABA release in the hippocampus.. Methods: For behavioural assessment, saline or ...
Both standard and v3 isoforms of CD44 were overexpressed in TamR cells at both gene and protein levels (mean fold increase in CD44s protein (TamR versus MCF7): 4.26 ± 1.2, P , 0.05). Moreover, CD44s and v3 colocalised with Her2 and Her3 receptors at the cell surface and were also detectable in Her2/Her3 cellular immunoprecipitates. Treatment of TamR cells with heregulin resulted in phosphorylation of erbB receptors together with a number of downstream signalling intermediates, including Akt, Src and FAK, and resulted in enhanced cellular migration. Significantly, heregulin-induced intracellular signalling was dramatically reduced in cells in which the expression of CD44 was suppressed (via siRNA), with a corresponding loss of heregulin-induced migratory behaviour (mean fold change in cell migration versus untreated control: 6.7 ± 1.1, P , 0.05 (heregulin beta 1); 1.8 ± 0.9 (CD44 siRNA); 1.47 ± 0.6, P , 0.05 (heregulin beta 1 + CD44 siRNA)). ...
Corfas G., Fischbach G.D.. ARIA is a glycoprotein purified from chick brain on the basis of its ACh receptor-inducing activity (ARIA). In this study we present evidence that ARIA increases the number of voltage-gated sodium channels in chick muscle as well as the number of ACh receptors (AChRs). Exposure of chick myotubes to ARIA increased by twofold the number of 3H-saxitoxin binding, an effect that is comparable to the increase of AChRs assayed by 125I-alpha-bungarotoxin (125I-alpha-BTX) binding. We also documented effects of ARIA on myoblasts: the number of 125I-alpha-BTX binding sites in the mononucleated muscle cells was increased by 1.5-fold, and the peak TTX-sensitive inward currents increased by the same amount. No change was detected in the voltage dependence of channel activation, in mean channel current, or in mean channel open time. Thus, the Na+ channel is the first molecule, other than AChR subunits, whose expression has been shown to be induced by ARIA. Since sodium channels are ...
Fusion protein amino acids 1-75 (membrane-associated N-terminus) of human Neuregulin-1 (also known as NRG1, Neu differentiation factor, NDF, Heregulin, HRG, HGL, Breast cancer cell differentiation factor p45, Acetylcholine receptor-inducing activity, ARIA, Glial growth factor, GGF, Sensory and motor-neuron-derived factor or SMDF, accession number Q96IB3); Mouse: 85% identity (64/75 amino acids identical); Rat: 82% identity (63/76 amino acids identical). ...
We previously demonstrated that neuregulin-1 (NRG-1) was neuroprotective in rats following ischemic stroke. Neuroprotection by NRG-1 was associated with the suppression of pro-inflammatory gene expression in brain tissues. Over-activation of brain microglia can induce pro-inflammatory gene expression by activation of transcriptional regulators following stroke. Here, we examined how NRG-1 transcriptionally regulates inflammatory gene expression by computational bioinformatics and in vitro using microglial cells. To identify transcriptional regulators involved in ischemia-induced inflammatory gene expression, rats were sacrificed 24 h after middle cerebral artery occlusion (MCAO) and NRG-1 treatment. Gene expression profiles of brain tissues following ischemia and NRG-1 treatment were examined by microarray technology. The Conserved Transcription Factor-Binding Site Finder (CONFAC) bioinformatics software package was used to predict transcription factors associated with inflammatory genes induced
We investigated the effects of deletion of two genes relevant to schizophrenia on cognitive tasks known to be disrupted in the disorder. The effect of deletion of the dopamine D2 receptor (D2R) and trans membrane (TM) domain Neuregulin-1 (Nrg-1) receptor were investigated in mediating disruptions in cognitive processes in an animal model of schizophrenia. The role of the D2R in an attentional model of sensorimotor gating was assessed. PPI was attenuated in D2R knock out (KO), in a one day sensorimotor gating task. In a one day PPI test protocol, amphetamine disruptions on PPI were spared in D2R WT and KO mice. Following on from previous reports of disrupted LI by a single low dose amphetamine injection, separated by 24h interval, we established a single vs. two low dose PPI protocol in order to facilitate a direct comparison of amphetamine induced disruption in LI with PPI. A one injection (prior to test only) vs. two injection (prior to habituation and prior to test) task was established. In ...
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Mitogen-induced changes in the actin cytoskeleton are accompanied by changes in the tyrosine phosphorylation of several proteins in focal adhesions. In this study, we have investigated the role of RAFTK (also termed Pyk2/CAK-β), a cytoplasmic tyrosine kinase related to focal adhesion kinase (FAK), in heregulin-mediated signal transduction in breast cancer cells. Stimulation of T47D cells with heregulin (HRG) induced the tyrosine phosphorylation of RAFTK and the formation of a multiprotein complex. Maximal phosphorylation of the proteins participating in this complex occurred within 2 h of HRG stimulation. Analyses of the members of the HRG-stimulated complex revealed that RAFTK associated with p190 RhoGAP (p190), RasGAP, c-Abl as well as with the focal adhesion molecules p130cas and paxillin. c-Abl was found to be associated with RAFTK through the region of RAFTK containing amino acids 419-1009. Site-directed mutagenesis of Y881 aa within the RAFTK sequence abolished the binding of RAFTK to ...
ARIA, or acetylcholine receptor-inducing activity, is a polypeptide that stimulates the synthesis of acetylcholine receptors in skeletal muscle. Here we demonstrate that the ability of ARIA to induce phosphorylation of its receptor in muscle is blocked by highly charged glycosaminoglycans. ARIA constructs lacking the NH2-terminal portion, containing an immunoglobulin-like domain, are fully active and are not inhibited by glycosaminoglycans. Limited proteolysis of ARIA with subtilisin blocks the glycosaminoglycan interaction by degrading this NH2-terminal portion, but preserves the active, EGF-like domain. We also show that ARIA can be released from freshly dissociated cells from embryonic chick spinal cord and cerebellum by either heparin, high salt or limited proteolysis with subtilisin, suggesting that ARIA is bound to the extracellular matrix through charged interactions. We present a model of how ARIA may be stored in extracellular matrix at developing synapses and how its release may be ...
3789 Epidermal Growth Factor-related ligands (EGF) and their cognate type-1 transmembrane receptors (ErbB/HER1-4) have been determined to play a key role in many normal cellular signalling processes. There are eleven known EGF ligands, of which the neuregulin genes (NRG1-4) are a new sub-family. Neuregulins interact specifically with two of the four HER receptors; HER3 and HER4 in a complex manner that results ultimately in altered gene expression. Change in the expression of EGF-ligands and/or their receptors can cause cell proliferation, which contributes considerably to the aetiology and progression of many human cancers including breast, lung, prostate and colon.. The Neuregulin-3 gene, encodes a soluble secreted ligand, which binds to and activates the HER4 receptor. Expression of NRG-3 mRNA has been observed in the CNS, testis and breast and has also been associated with breast carcinogenesis and mammary gland development. The counterpart Neuregulin-1, 2 and 4 genes are highly susceptible ...
The major findings of this study are that mice with only one functional allele of the type III Nrg1 gene lack multiple aspects of excitatory synaptic plasticity in cortical-BLA circuits. Specifically, in type III Nrg1 heterozygotes, cortical-BLA synapses failed to potentiate in response to either HFS (Fig. 3 vs Fig. 4) or TBS in combination with brief exposure to low concentrations of nicotine, conditions that reliably induce sustained potentiation of synaptic transmission in WT littermates (Fig. 7) (Jiang and Role, 2008). This latter result was phenocopied in α7*nAChR heterozygotes (Fig. 7). In addition to these dramatic changes in plasticity, more subtle differences between type III Nrg1 heterozygotes and WT mice were seen in terms of baseline synaptic transmission. Most notably, we found a decrease in NMDA/AMPA ratio, largely driven by increased AMPA receptor-mediated synaptic current amplitude (Fig. 2), an accelerated rate of decay of mEPSCs (Fig. 1), and a failure of nicotine to increase ...
Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction (MI). Increasing evidence indicates that neuregulin-1 (NRG-1) improves cardiac function following heart failure. Since its impact on cardiac function and neural remodeling post-MI is poorly understood, we aimed to investigate the role of NRG-1 in autonomic nervous system remodeling post-MI. Forty-five Sprague-Dawley rats were equally randomized into three groups: sham (with the left anterior descending coronary artery exposed but without ligation), MI (left anterior descending coronary artery ligation), and MI plus NRG-1 (left anterior descending coronary artery ligation followed by intraperitoneal injection of NRG-1 (10 μg/kg, once daily for 7 days ...
Does anyone out there know if there is a commercial supplier of an antibody raised against the growth factor ligand heregulin ? Any help or advice would be greatly appreciated.... Jonathan Harris Hammersmith Hospital London UK ...
RT @BeaudinLab: Also, my new lab at @UofUMedicine will be recruiting 2-3 new post docs! If you know anyone with passion and an interest in… about 2 weeks ago ...
Agarwal, A.; Zhang, M.; Trembak-Duff, I.; Unterbarnscheidt, T.; Radyushkin, K.; Dibaj, P.; de Souza, D. M.; Boretius, S.; Brzózka, M. M.; Steffens, H. et al.; Berning, S.; Teng, Z.; Gummert, M. N.; Tantra, M.; Guest, P. C.; Willig, K. I.; Frahm, J.; Hell, S. W.; Bahn, S.; Rossner, M. J.; Nave, K. A.; Ehrenreich, H.; Zhang, W.; Schwab, M. H.: Dysregulated expression of Neuregulin-1 by cortical pyramidal neurons disrupts synaptic plasticity. Cell Reports 8 (4), S. 1130 - 1145 (2014 ...
Agarwal, A.; Zhang, M.; Trembak-Duff, I.; Unterbarnscheidt, T.; Radyushkin, K.; Dibaj, P.; de Souza, D. M.; Boretius, S.; Brzózka, M. M.; Steffens, H. et al.; Berning, S.; Teng, Z.; Gummert, M. N.; Tantra, M.; Guest, P. C.; Willig, K. I.; Frahm, J.; Hell, S. W.; Bahn, S.; Rossner, M. J.; Nave, K. A.; Ehrenreich, H.; Zhang, W.; Schwab, M. H.: Dysregulated expression of Neuregulin-1 by cortical pyramidal neurons disrupts synaptic plasticity. Cell Reports 8 (4), S. 1130 - 1145 (2014 ...
J:60159 Wolpowitz D, Mason TB, Dietrich P, Mendelsohn M, Talmage DA, Role LW, Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses. Neuron. 2000 Jan;25(1):79-91 ...
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Anti-Neuregulin-1 SMDF polyclonal antibody (STJ94419) was developed using a synthesized peptide derived from the N-terminal region of human Neuregulin-1 SMDF at AA range: 1-80. This antibody is applicable for use in western blot, immunohistochemistry, imm
Inhibition of cardiac ErbB2 signaling in vivo leads to cardiomyopathy in the presence of anthracyclines or pressure overload but also in the apparent absence of any stress factor on the heart. Trastuzumab initially caused cardiac dysfunction in up to 7% of patients when used as a single agent and in up to 27% when combined with anthracyclines. Severe CHF, New York Heart Association class III and IV, occurred in 16% of patients treated with a combination of trastuzumab and anthracyclines.46 More recent studies incorporating well-designed prospective cardiac monitoring suggest a lower incidence of symptomatic CHF (up to 4% for the trastuzumab-anthracycline combination). Nevertheless, asymptomatic cardiac dysfunction still occurs in ,14% of patients receiving trastuzumab with anthracyclines and in 7% receiving trastuzumab alone.47. Despite extensive research, cardiotoxic effects of trastuzumab, and ErbB2 inhibition in general, have remained difficult to explain. Trastuzumab cardiotoxicity appears ...
Neuregulin-1β (NRG-1β) is a member of the epidermal growth factor family released from cardiac microvascular endothelial cells that acts via a set of tyrosine kinase receptors (ErbB2, ErbB3, ErbB4) to promote growth, differentiation, and survival of cardiomyocytes. NRG-1/ErbB signaling is indispensable both in the cardiac development and in the adult heart. It regulates myocardial performance and sympatovagal balance, and may exert beneficial cardioprotective effects. In animal studies, the depletion of this pathway can induce heart failure, whereas an administration of recombinant NRG-1β can improve cardiac function and increase survival in different experimental models of cardiomyopathy. The presented study is the first to explore the significance of circulating NRG-1β in human heart disease, and provides evidence on the role of NRG-1/ErbB signaling in human heart failure, indicating that circulating NRG-1β might serve as a novel biomarker to assess prognosis in patients with heart ...
J:91711 Miyazaki Y, Nakanishi Y, Hieda Y, Tissue interaction mediated by neuregulin-1 and ErbB receptors regulates epithelial morphogenesis of mouse embryonic submandibular gland. Dev Dyn. 2004 Aug;230(4):591-6 ...
hMena (ENAH), an actin regulatory protein involved in the control of cell motility and adhesion, is modulated during human breast carcinogenesis. In fact, whereas undetectable in normal mammary epithelium, hMena becomes overexpressed in high-risk benign lesions and primary and metastatic tumors. In vivo, hMena overexpression correlates with the HER-2+/ER−/Ki67+ unfavorable prognostic phenotype. In vitro, neuregulin-1 up-regulates whereas Herceptin treatment down-modulates hMena expression, suggesting that it may couple tyrosine kinase receptor signaling to the actin cytoskeleton. Herein, we report the cloning of hMena and of a splice variant, hMena+11a, which contains an additional exon corresponding to 21 amino acids located in the EVH2 domain, from a breast carcinoma cell line of epithelial phenotype. Whereas hMena overexpression consistently characterizes the transformed phenotype of tumor cells of different lineages, hMena+11a isoform is concomitantly present only in epithelial tumor cell ...
Myc-DDK-tagged ORF clone of Homo sapiens neuregulin 1 (NRG1), transcript variant ndf43c as transfection-ready DNA - 10 µg - OriGene - cdna clones
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The new NRG PRO is a quick handling fast wing for pilots who want the speed and tight turns. Based on very successful NRG design, the NRG PRO provides solid base to take you to the next level - at competitions or just for fun. The NRG PRO was designed for pylon racing pilots, it is ideal for experienced pilot looking for super quick handling, combined with stability, and excellent launch characteristics. NRG PRO stability through the entire speed range makes it an ideal choice for fast XC flights ...
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The selective erbB2 antagonist AG825 dampens the NRG1α-induced MRVA.Administration of AG825 in DMSO vehicle (n = 5) caused a robust, dose-dependent decreas
A Wal-Mart vice president has suggested to the companys board of directors that it could hold down spending on health care and benefits by hiring more part-time workers and encouraging healthier, more productive employees, according to an internal memo obtained by CNN.
I was watching a television show today, and one of the characters--a surgeon, posed like a super-hero before performing a surgery. They said it inspires confidence and improves performance. I had to look it up, and sure enough:
Darius, Paul Check, i do not know if you know who he is? But he made a comment once that made an inpact on me many years ago, he said something like ".... Read More ...
n result calls ## [1,] 1 1 1 ## [2,] 2 2 3 ## [3,] 3 3 5 ## [4,] 4 5 9 ## [5,] 5 8 15 ## [6,] 6 13 25 ## [7,] 7 21 41 ## [8,] 8 34 67 ## [9,] 9 55 109 ## [10,] 10 89 177 ## [11,] 11 144 287 ## [12,] 12 233 465 ## [13,] 13 377 753 ## [14,] 14 610 1219 ## [15,] 15 987 1973 ## [16,] 16 1597 ...
Schwann cells can form Remak bundles ensheathing multiple, small unmyelinated axons or can form thick or thin myelin sheaths around axons. Generally, the size of the axons correlates with their ensheathment or myelination: the thicker the axon, the thicker the myelin. Taveggia et al. now show that neuregulin-1 (NRG-1) type III serves as a signal to the Schwann cells, with low concentrations of NRG-1 type III in the neuron leading to ensheathment and high concentrations leading to thick myelination. In cultures of rat Schwann cells with dorsal root ganglion (DRG) neurons from wild-type or NRG1 type III -/- mice, the Schwann cells robustly myelinated the wild-type neurites but failed to myelinate the NRG-1 type III-deficient neurites. Forced expression of NRG-1 type III in the deficient DRG cells allowed the Schwann cells to myelinate the neurites, and in some cases the myelin was as much as twice as thick as that surrounding the wild-type neurites. Analysis of the abundance of NRG-1 type III in ...
Title:Neurobehavioral Differences Between Mice Receiving Distinct Neuregulin Variants as Neonates; Impact on Sensitivity to MK-801. VOLUME: 15 ISSUE: 3. Author(s):T. Kato, Y. Abe, S. Hirokawa, Y. Iwakura, M. Mizuno, H. Namba and H. Nawa. Affiliation:Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Niigata 951-8585, Japan.. Keywords:Behavior, MK-801, Neuregulin-1, NMDA receptor, hearing, schizophrenia.. Abstract:Neuregulin-1 (NRG1) is a well-recognized risk gene for schizophrenia and is often implicated in the neurodevelopmental hypothesis of this illness. Alternative splicing and proteolytic processing of the NRG1 gene produce more than 30 structural variants; however, the neuropathological roles of individual variants remain to be characterized. On the basis of the neurodevelopmental hypothesis of schizophrenia, we administered eNRG1 (0.1~1.0 μg/g), a core epidermal growth factor-like (EGF) domain common for all splicing NRG1 variants, ...
The family of Neuregulins (NRG), growth factors like epidermal growth factor, is known to induce growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells. This family comprises four members, being NRG1 the most largely studied, particularly at the cardiovascular level. The biological effects of NRG1 in the adult heart are mediated by the tyrosine kinase receptors ErbB. In the adult heart, NRG1 is expressed by cells of the endocardial endothelium and the cardiac microvascular endothelium, and the receptors ErbB2/ErbB4 are expressed by ventricular cardiomyocytes and are located in T-tubule system and intercalated disks in close proximity to the system components of excitation-contraction coupling. The importance of the NRG/ErbB signaling axis at the cardiovascular level became evident after discovering that patients treated with trastuzumab (inhibitory antibody against ErbB2, used in the treatment of breast cancer) can develop ventricular dysfunction and have higher ...
The small GTPase Rac1 has been widely implicated in mammary tumorigenesis and metastasis. Previous studies established that stimulation of ErbB receptors in breast cancer cells activates Rac1 and enhances motility via the Rac-GEF P-Rex1. As the Jak2/Stat3 pathway has been shown to be functionally associated with ErbB receptors, we asked if this pathway could mediate P-Rex1/Rac1 activation in response to ErbB ligands. Here we found that the anticancer agent cucurbitacin I, a Jak2 inhibitor, reduced the activation of Rac1 and motility in response to the ErbB3 ligand heregulin in breast cancer cells. However, Rac1 activation was not affected by Jak2 or Stat3 RNAi, suggesting that the effect of cucurbitacin I occurs through a Jak2-independent mechanism. Cucurbitacin I also failed to affect the activation of P-Rex1 by heregulin. Subsequent analysis revealed that cucurbitacin I strongly activates RhoA and the Rho effector ROCK in breast cancer cells and induces the formation of stress fibers. ...
Intracellular expression of antibodies provides a novel approach for the manipulation of biochemical processes in intact cells. We have used this approach to test two alternative strategies for the...
Loeb JA, Hmadcha A, Fischbach GD, Land SJ, and Zakarian VL (2002). Neuregullin expression at neuromuscular synapses is modulated by synaptic activity and neurotrophic factors. J. of Neurosci. 22(6). Mann MA, Knipe DM, Fischbach GD, Fields BN (2002). Type 3 reovirus neuroinvation after intramuscular inoculation: direct invasion of nerve terminals and age-dependent pathogenesis. Virology Nov 25:303(2):222-31. Jacobson C, Duggan D, and Fischbach G, (2004) Neuregulin induces the expression of transcription factors and myosin heavy chains typical of muscle spindles in cultured human muscle. PNAS 101(33): 12218-12223. Fischbach G, and Fischbach R, (2004) Stem Cells: science, policy, and ethics. J. of Clinical Investigation 114(10): 1364-1370. Fischbach RL, and Fischbach GD, (2005) The brain doesnt lie. Am J Bioeth Spring 5(2): 54-55. Liu Y, Ford BD, Mann MA, and Fischbach GD, (2005) Neuregulin-1 increases the proliferation of neuronal progenitors from embryonic neural stem cells. Dev Biol Jul ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The article suggests only one route to finding truly novel mechanisms - genetics. In the past few years, there have been many genetic studies trying to find genes which cause mental illnesses. Some of them have identified risk genes which seem to imply new biological pathways. For example, the current orthodoxy is that schizophrenia is caused by abnormalities in the brains dopamine system. But the gene most strongly implicated in schizophrenia is called "neuregulin-1", and it has nothing to do with dopamine. Thats interesting but unfortunately ...
Function Neuregulin 2 (NRG2) is a novel member of the neuregulin family of growth and differentiation factors. Through interaction with the ErbB family of receptors, NRG2 induces the growth and differentiation of epithelial, neuronal, glial, and other types of cells. The gene consists of 12 exons and the genomic structure is similar to that of neuregulin 1 (NRG1), another member of the neuregulin family of ligands. NRG1 and NRG2 mediate distinct biological processes by acting at different sites in tissues and eliciting different biological responses in cells. The gene is located close to the region for demyelinating Charcot-Marie-Tooth disease locus, but is not responsible for this disease. Alternative transcripts encoding distinct isoforms have been described.[1] ...
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p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
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I grew up in a suburb of New York City, so we probably had more channels than people in other parts of the country, but we still didnt have shows broadcast all day. I could be wrong about this, but I think the nightly news was only on for 15 minutes each evening. The Today Show didnt even come on the air until 1952. We received most of our news from newspapers ...
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Armando Arias is the author of this article in the Journal of Visualized Experiments: Reverse Genetics Mediated Recovery of Infectious Murine Norovirus
4 detailed and in-depth reviews for NRG Max: ----Introduction---- 39 year old gym rat ... Lately I have been going to the gym even more since I started doing pre-workouts ... Im just almost never out of energy. I bought this pre-workout because it has almost everything that I would want with clinically recommended doses. What stood out from