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Julie Ry Gustafsson, Georgia Katsioudi, Matilda Degn, Patrick Ejlerskov, Shohreh Issazadeh-Navikas, Birgitte Rahbek Kornum
Major Histocompability Complex I (MHC-I) molecules present cellularly derived peptides to the adaptive immune system. Generally MHC-I is not expressed on healthy post-mitotic neurons in the central nervous system, but it is known to increase upon immune activation such as viral infections and also during neurodegenerative processes. MHC-I expression is known to be regulated by the DNA methyltransferase DNMT1 in non-neuronal cells. Interestingly DNMT1 expression is high in neurons despite these being non-dividing...
July 3, 2018: Molecular Brain
Dong-Cheol Kim, Tran Hong Quang, Hyuncheol Oh, Youn-Chul Kim
Excessive microglial stimulation has been recognized in several neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotropic lateral sclerosis (ALS), HIV-associated dementia (HAD), multiple sclerosis (MS), and stroke. When microglia are stimulated, they produce proinflammatory mediators and cytokines, including nitric oxide (NO) derived from inducible NO synthase (iNOS), prostaglandin E2 (PGE₂) derived from cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-12 (IL-12), and interleukin-6 (IL-6)...
December 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Taiwo Olayemi Elufioye, Tomayo Ireti Berida, Solomon Habtemariam
Neuroprotection is the preservation of the structure and function of neurons from insults arising from cellular injuries induced by a variety of agents or neurodegenerative diseases (NDs). The various NDs including Alzheimer's, Parkinson's, and Huntington's diseases as well as amyotropic lateral sclerosis affect millions of people around the world with the main risk factor being advancing age. Each of these diseases affects specific neurons and/or regions in the brain and involves characteristic pathological and molecular features...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Medhi Wangpaichitr, Chunjing Wu, Ying Ying Li, Dan J M Nguyen, Hande Kandemir, Sumedh Shah, Shumei Chen, Lynn G Feun, Jeffrey S Prince, Macus T Kuo, Niramol Savaraj
Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter...
July 25, 2017: Oncotarget
Parimala Narne, Vimal Pandey, Praveen Kumar Simhadri, Prakash Babu Phanithi
Neurodegeneration is a salient feature of chronic refractory brain disorders like Alzheimer's, Parkinson's, Huntington's, amyotropic lateral sclerosis and acute conditions like cerebral ischemia/reperfusion etc. The pathological protein aggregates, mitochondrial mutations or ischemic insults typifying these disease conditions collude with and intensify existing oxidative stress and attendant mitochondrial dysfunction. Interlocking these mechanisms is poly(ADP-ribose) polymerase (PARP-1) hyperactivation that invokes a distinct form of neuronal cell death viz...
March 2017: Seminars in Cell & Developmental Biology
Smrati Bajpai, Nikhil Bhasin, Kavita Joshi, Milind Y Nadkar, A R Pazare
The co-occurrence of myasthenia gravis with motor neurone disease is not a very common association and may pose problem and confusion in the minds of the treating physician because of the gamut of neurological symptoms. This case intends to highlight these dilemmas.
March 2016: Journal of the Association of Physicians of India
Ross Ferguson, Eleni Serafeimidou-Pouliou, Vasanta Subramanian
The hexanucleotide repeat in the first intron of the C9orf72 gene is the most significant cause of amyotropic lateral sclerosis as well as some forms of fronto-temporal dementia. The C9orf72 protein has been previously reported to be expressed in post-mortem human brain as well as in late embryonic and some postnatal stages in mice. Herein, we present a detailed study of the distribution of C9orf72 protein in the embryonic, postnatal and adult mouse brain, spinal cord as well as during the differentiation of P19 embryonal carcinoma cells to neurons including motor neurons...
December 2016: Journal of Anatomy
Alejandro F De Nicola, Florencia Coronel, Laura I Garay, Gisella Gargiulo-Monachelli, Maria Claudia Gonzalez Deniselle, Susana L Gonzalez, Florencia Labombarda, Maria Meyer, Rachida Guennoun, Michael Schumacher
Substantial evidence supports that progesterone exerts many functions in the central and peripheral nervous system unrelated to its classical role in reproduction. In this review we first discussed progesterone effects following binding to the classical intracellular progesterone receptors A and B and several forms of membrane progesterone receptors, the modulation of intracellular signalling cascades and the interaction of progesterone reduced metabolites with neurotransmitter receptors. We next described our results involving animal models of human neuropathologies to elucidate the protective roles of progesterone...
December 2013: CNS & Neurological Disorders Drug Targets
Stacey S Willard, Shahriar Koochekpour
Glutamate, a nonessential amino acid, is the major excitatory neurotransmitter in the central nervous system. As such, glutamate has been shown to play a role in not only neural processes, such as learning and memory, but also in bioenergetics, biosynthetic and metabolic oncogenic pathways. Glutamate has been the target of intense investigation for its involvement not only in the pathogenesis of benign neurodegenerative diseases (NDDs) such as Parkinson's disease, Alzheimer's disease, schizophrenia, multiple sclerosis, and amyotropic lateral sclerosis (ALS), but also in carcinogenesis and progression of malignant diseases...
2013: International Journal of Biological Sciences
Sanjit Kumar Dhar, Jiayu Zhang, Jozsef Gal, Yong Xu, Lu Miao, Bert C Lynn, Haining Zhu, Edward J Kasarskis, Daret K St Clair
AIMS: FUsed in sarcoma (FUS) is a multifunctional DNA/RNA-binding protein that possesses diverse roles, such as RNA splicing, RNA transport, DNA repair, translation, and transcription. The network of enzymes and processes regulated by FUS is far from being fully described. In this study, we have focused on the mechanisms of FUS-regulated manganese superoxide dismutase (MnSOD) gene transcription. RESULTS: Here we demonstrate that FUS is a component of the transcription complex that regulates the expression of MnSOD...
April 1, 2014: Antioxidants & Redox Signaling
Kang-Woo Lee, Hye Min Ji, Dong Woung Kim, Sun-Mi Choi, Sungchul Kim, Eun Jin Yang
ETHNOPHARMACOLOGICAL RELEVANCE: Hominis placenta (HP) dried placenta extracted from pregnant women after delivery has been widely used to treat chronic inflammatory diseases. HP has been reported to be effective to alleviate the arthritic symptoms by modulating the expression of inflammatory factors in adjuvant-induced arthritis rats. However, the mechanism of action of HP is unknown. Neuroinflammation has been implicated in the pathogenesis of several neurodegenerative disease, including Alzheimer's disease (AD), Parkinson's disease (PD) and amyotropic lateral sclerosis (ALS)...
May 20, 2013: Journal of Ethnopharmacology
Warren E Hochfeld, Shirley Lee, David C Rubinsztein
There is accumulating evidence that aggregating, misfolded proteins may have an impact on autophagic function, suggesting that this could be a secondary pathological mechanism in many diseases. In this review, we focus on the role of autophagy in four major neurodegenerative diseases: Alzheimer disease (AD), Huntington's disease (HD), Parkinson's disease (PD) and amyotropic lateral sclerosis.
May 2013: Acta Pharmacologica Sinica
M Casula, K Steentjes, E Aronica, B M van Geel, D Troost
Post-polio syndrome (PPS) develops in approximately 30% of polio survivors several decades after the acute attack of paralytic poliomyelitis. Some of these patients develop post-poliomyelitis muscular atrophy (PPMA) which is characterized by a slowly progressive muscle weakness. Due to its clinicopathological features, investigators have often studied PPS and PPMA in association with amyotrophic lateral sclerosis (ALS), the underlying hypothesis being an increased risk of developing ALS from a prior acute paralytic poliomyelitis...
May 2011: Clinical Neuropathology
Toshio Shimizu, Michiyuki Hayashi, Akihiro Kawata, Toshio Mizutani, Kazuhiko Watabe, Shiro Matsubara
Amyotrophic lateral sclerosis (ALS) shows peculiar abnormalities of the autonomic nervous system, including sympathetic hyperactivity, which might result in sudden death. In general, the sympathetic hyperactivity could be caused by disruption of vagal inhibition. Our objective was to evaluate the vagus nerve morphometrically in autopsy cases of ALS with sympathetic hyperactivity and circulatory collapse (CC). We investigated 10 autopsied ALS patients, six of whom had exhibited autonomic storms or CC. We also examined 10 patients without ALS as controls, and one patient with Guillain-Barré syndrome (GBS) who died from CC, for comparison...
September 2011: Amyotrophic Lateral Sclerosis
Mustafa Nazıroğlu
The Na+ and Ca(2+)-permeable melastatin related transient receptor potential 2 (TRPM2) channels can be gated either by ADP-ribose (ADPR) in concert with Ca(2+) or by hydrogen peroxide (H(2)O(2)), an experimental model for oxidative stress, binding to the channel's enzymatic Nudix domain. Since the mechanisms that lead to TRPM2 gating in response to ADPR and H(2)O(2) are not understood in neuronal cells, I summarized previous findings and important recent advances in the understanding of Ca(2+) influx via TRPM2 channels in different neuronal cell types and disease processes...
March 2011: Neurochemical Research
Thomas W Gould, Ronald W Oppenheim
The modest effects of neurotrophic factor (NTF) treatment on lifespan in both animal models and clinical studies of Amyotropic Lateral Sclerosis (ALS) may result from any one or combination of the four following explanations: 1.) NTFs block cell death in some physiological contexts but not in ALS; 2.) NTFs do not rescue motoneurons (MNs) from death in any physiological context; 3.) NTFs block cell death in ALS but to no avail; and 4.) NTFs are physiologically effective but limited by pharmacokinetic constraints...
June 24, 2011: Brain Research Reviews
Tiziana Bisogno, Vincenzo Di Marzo
The G-protein coupled receptors for Δ⁹-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB₁) and 2 (CB₂) and play important functions in degenerative and inflammatory disorders of the central nervous system. Whilst CB₁ receptors are mostly expressed in neurons, where they regulate neurotransmitter release and synaptic strength, CB₂ receptors are found mostly in glial cells and microglia, which become activated and over-express these receptors during disorders such as Alzheimer's disease, multiple sclerosis, amyotropic lateral sclerosis, Parkinson's disease, and Huntington's chorea...
November 2010: CNS & Neurological Disorders Drug Targets
E Zerovnik
The whole set of so-called >conformational< disorders, among them systemic amyloidoses, various dementias and other neurodegenerative diseases such as Parkinson's, Alzheimer's and amyotropic lateral sclerosis, may have similar molecular backgrounds: changes in protein conformation and aggregation lead to toxic amyloid oligomers and fibrils. The so called aggresomes in eukaryotes (equivalent to inclusion bodies in prokaryotes), located at the centriole by the nucleus and composed of aggregated proteins, are believed to sequester the toxic material...
February 2010: Current Alzheimer Research
Qiang Zhang, Liping Peng, Deren Zhang
Postherpetic neuralgia (PHN) is a chronic pain syndrome and one of the most common complications of herpes zoster. Although the pathophysiological mechanisms involved in PHN are still largely unknown, it seems reasonable to assume that there are lesions of the peripheral afferent pain pathways and inflammation-induced damage to afferent ganglia in the spinal cord. Growing body of evidence indicates that the glial cells, particularly microglia (CNS macrophages) and astrocytes are activated following peripheral and central noxious insult and their activation is thought to play an important role in central sensitization...
November 2009: Medical Hypotheses
Jyotshnabala Kanungo, Ya-li Zheng, Niranjana D Amin, Harish C Pant
The major priming event in neurodegeneration is loss of neurons. Loss of neurons by apoptotic mechanisms is a theme for studies focused on determining therapeutic strategies. Neurons following an insult, activate a number of signal transduction pathways, of which, kinases are the leading members. Cyclin-dependent kinase 5 (Cdk5) is one of the kinases that have been linked to neurodegeneration. Cdk5 along with its principal activator p35 is involved in multiple cellular functions ranging from neuronal differentiation and migration to synaptic transmission...
December 2009: Cellular and Molecular Neurobiology
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