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https://www.readbyqxmd.com/read/28644955/turning-on-proteasomes
#1
Jan Henrik Krahn, Farnusch Kaschani, Markus Kaiser
While proteasome inhibitors are now well-established research tools and chemotherapeutics, proteasome activators are much less explored. In this issue of Cell Chemical Biology, in a study from the groups of Berkers and Ovaa (Leestemaker et al., 2017), a chemical screen was used to identify a p38 MAPK inhibitor as a proteasome activator. This compound furthermore enhanced clearance of protein aggregates, thereby implicating alternative chemotherapeutic options for treating neurodegenerative diseases.
June 22, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28644490/potentiating-role-of-copper-on-spatial-memory-deficit-induced-by-beta-amyloid-and-evaluation-of-mitochondrial-function-markers-in-the-hippocampus-of-rats
#2
Ladan Behzadfar, Mohammad Abdollahi, Omid Sabzevari, Rohollah Hosseini, Ahmad Salimi, Parvaneh Naserzadeh, Mohammad Sharifzadeh, Jalal Pourahmad
Mounting evidence suggests that copper, a crucial element in normal brain function, plays an important role in the etiology of Alzheimer's disease, which is known as a neurodegenerative mitochondrial disorder. However, the precise mechanisms of its effects on cognitive and mitochondrial functions through the CNS have not been thoroughly recognized yet. In this study, we aimed to investigate the long-term (3-week) effects of copper sulfate (50, 100 and 200 mg kg(-1) day(-1)) exposure on learning and memory as well as on mitochondrial function in the hippocampus of rats in the presence and absence of beta amyloid (1 μg μl(-1) per side) intrahippocampally (IH)...
June 23, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28644434/ageing-and-hypoxia-cause-protein-aggregation-in-mitochondria
#3
Daniel M Kaufman, Xia Wu, Barbara A Scott, Omar A Itani, Marc R Van Gilst, James E Bruce, C Michael Crowder
Aggregation of cytosolic proteins is a pathological finding in disease states, including ageing and neurodegenerative diseases. We have previously reported that hypoxia induces protein misfolding in Caenorhabditis elegans mitochondria, and electron micrographs suggested protein aggregates. Here, we seek to determine whether mitochondrial proteins actually aggregate after hypoxia and other cellular stresses. To enrich for mitochondrial proteins that might aggregate, we performed a proteomics analysis on purified C...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644430/the-clinical-landscape-for-sma-in-a-new-therapeutic-era
#4
REVIEW
K Talbot, E F Tizzano
Despite significant advances in basic research, the treatment of degenerative diseases of the nervous system remains one of the greatest challenges for translational medicine. The childhood onset motor neuron disorder spinal muscular atrophy (SMA) has been viewed as one of the more tractable targets for molecular therapy, due to a detailed understanding of the molecular genetic basis of the disease. In SMA, inactivating mutations in the SMN1 gene can be partially compensated for by limited expression of SMN protein from a variable number of copies of the SMN2 gene, which provides both a molecular explanation for phenotypic severity and a target for therapy...
June 23, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28644409/quercetin-protects-obesity-induced-hypothalamic-inflammation-by-reducing-microglia-mediated-inflammatory-responses-via-ho-1-induction
#5
Jihyeon Yang, Chu-Sook Kim, Thai Hien Tu, Min-Seon Kim, Tsuyoshi Goto, Teruo Kawada, Myung-Sook Choi, Taesun Park, Mi-Kyung Sung, Jong Won Yun, Suck-Young Choe, Jee Hye Lee, Yeonsoo Joe, Hye-Seon Choi, Sung Hoon Back, Hun Taeg Chung, Rina Yu
Obesity-induced hypothalamic inflammation is characterized by activation of microglia, which are resident macrophages of the central nervous system, and is implicated in the derangement of energy homeostasis, metabolic complications, and neurodegenerative diseases. Quercetin, a naturally occurring flavonoid, is known to protect against oxidative stress and inflammation-related metabolic complications. Here, we demonstrate that quercetin reduces obesity-induced hypothalamic inflammation by inhibiting microglia-mediated inflammatory responses, and the beneficial action of quercetin is associated with heme oxygenase (HO-1) induction...
June 23, 2017: Nutrients
https://www.readbyqxmd.com/read/28644304/abnormal-retinal-reflectivity-to-short-wavelength-light-in-type-2-idiopathic-macular-telangiectasia
#6
Ferenc B Sallo, Irene Leung, Meike Zeimer, Traci E Clemons, Adam M Dubis, Marcus Fruttiger, Daniel Pauleikhoff, Emily Y Chew, Catherine Egan, Tunde Peto, Alan C Bird
PURPOSE: Macular telangiectasia Type 2 (MacTel) is a bilateral, progressive, potentially blinding retinal disease characterized by vascular and neurodegenerative signs, including an increased parafoveal reflectivity to blue light. Our aim was to investigate the relationship of this sign with other signs of macular telangiectasia Type 2 in multiple imaging modalities. METHODS: Participants were selected from the MacTel Type 2 study, based on a confirmed diagnosis and the availability of images...
June 21, 2017: Retina
https://www.readbyqxmd.com/read/28644111/visual-dot-interaction-with-short-term-memory
#7
Faustin Armel Etindele Sosso
AIM: Many neurodegenerative diseases have a memory component. Brain structures related to memory are affected by environmental stimuli, and it is difficult to dissociate effects of all behavior of neurons. MATERIALS & METHODS: Here, visual cortex of mice was stimulated with gratings and dot, and an observation of neuronal activity before and after was made. Bandwidth, firing rate and orientation selectivity index were evaluated. RESULTS: A primary communication between primary visual cortex and short-term memory appeared to show an interesting path to train cognitive circuitry and investigate the basics mechanisms of the neuronal learning...
June 23, 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/28643388/a-longitudinal-item-response-theory-model-to-characterize-cognition-over-time-in-elderly-subjects
#8
Marc Vandemeulebroecke, Björn Bornkamp, Tillmann Krahnke, Johanna Mielke, Andreas Monsch, Peter Quarg
For drug development in neurodegenerative diseases such as Alzheimer's disease, it is important to understand which cognitive domains carry most information on earliest signs of cognitive decline, and which subject characteristics are associated with a faster decline. A longitudinal Item Response Theory (IRT) model was developed for the Basel Study of the Elderly, in which the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (with additions) and the California Verbal Learning Test were measured on 1750 elderly subjects for up to 13...
June 23, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28643372/fine-tuning-perk-signaling-for-neuroprotection
#9
REVIEW
Mark Halliday, Daniel Hughes, Giovanna Mallucci
Protein translation and folding are tightly controlled processes in all cells, by proteostasis, an important component of which is the unfolded protein response (UPR). During periods of endoplasmic reticulum stress due to protein misfolding, the UPR activates a coordinated response in which the PERK branch activation restricts translation, while a variety of genes involved with protein folding, degradation, chaperone expression and stress responses are induced through signaling of the other branches. Chronic overactivation of the UPR, particularly the PERK branch is observed in the brains of patients in a number of protein misfolding neurodegenerative diseases, including Alzheimer's, and Parkinson's diseases and the taopathies...
June 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28643167/microbiome-probiotics-and-neurodegenerative-diseases-deciphering-the-gut-brain-axis
#10
REVIEW
Susan Westfall, Nikita Lomis, Imen Kahouli, Si Yuan Dia, Surya Pratap Singh, Satya Prakash
The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health...
June 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28642891/safety-tolerability-of-the-anti-semaphorin-4d-antibody-vx15-2503-in-a-randomized-phase-1-trial
#11
Christopher LaGanke, Lawrence Samkoff, Keith Edwards, Lily Jung Henson, Pavle Repovic, Sharon Lynch, Lael Stone, David Mattson, Aaron Galluzzi, Terrence L Fisher, Christine Reilly, Laurie A Winter, John E Leonard, Maurice Zauderer
OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of VX15/2503 in a randomized, single-dose, dose-escalation, double-blind, placebo-controlled study enrolling adult patients with MS. METHODS: Single IV doses of VX15/2503 or placebo were administered. Ten patients each were randomized (4:1 randomization ratio) into 5 ascending dose cohorts of 1, 3, 6, 10, or 20 mg/kg. Safety, immunogenicity, PK/PD, MRI, ECG, and lymphocyte subset levels were evaluated...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28642806/the-efficacy-of-epigallocatechin-3-gallate-green-tea-in-the-treatment-of-alzheimer-s-disease-an-overview-of-pre-clinical-studies-and-translational-perspectives-in-clinical-practice
#12
REVIEW
Marco Cascella, Sabrina Bimonte, Maria Rosaria Muzio, Vincenzo Schiavone, Arturo Cuomo
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common form of dementia characterized by cognitive and memory impairment. One of the mechanism involved in the pathogenesis of AD, is the oxidative stress being involved in AD's development and progression. In addition, several studies proved that chronic viral infections, mainly induced by Human herpesvirus 1 (HHV-1), Cytomegalovirus (CMV), Human herpesvirus 2 (HHV-2), and Hepatitis C virus (HCV) could be responsible for AD's neuropathology...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28642732/autonomic-function-impairment-and-brain-perfusion-deficit-in-parkinson-s-disease
#13
Wei-Che Lin, Pei-Chin Chen, Chih-Cheng Huang, Nai-Wen Tsai, Hsiu-Ling Chen, Hung-Chen Wang, Kun-Hsien Chou, Meng-Hsiang Chen, Yi-Wen Chen, Cheng-Hsien Lu
INTRODUCTION: Autonomic disorders have been recognized as important Parkinson's disease (PD) components. Some vulnerable structures are related to the central autonomic network and have also been linked to autonomic function alterations. The aims of the study are to evaluate the severity of the autonomic dysfunction and the cortical hypoperfusion using arterial spin labeling (ASL) MRI. And then, possible relationships of significant between-group differences in perfusion pattern to clinical variables and autonomic functions were examined to determine the pharmaceutical effects of dopaminergic treatment on cerebral blood flow (CBF) in patients with PD...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28642233/sembragiline-a-novel-selective-monoamine-oxidase-type-b-inhibitor-for-the-treatment-of-alzheimer-s-disease
#14
Edilio Borroni, Bernd Bohrmann, Fiona Grueninger, Eric Prinssen, Stephane Nave, Hansruedi Loetscher, Shankar J Chinta, Subramanian Rajagopalan, Anand Rane, Almas Siddiqui, Bart Ellenbroek, Juerg Messer, Axel Pahler, Julie K Anderson, Rene Wyler, Andrea M Cesura
Monoamine oxidase B (MAO-B) has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. Increased MAO-B expression in astroglia has been observed adjacent to amyloid plaques in AD patient brains. This phenomenon is hypothesised to lead to increased production of hydrogen peroxide and reactive oxygen species (ROS), thereby contributing to AD pathology. Therefore, reduction of ROS-induced oxidative stress via inhibition of MAO-B activity may delay the progression of the disease...
June 22, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28642137/overexpression-cdc42-attenuates-isoflurane-induced-neurotoxicity-in-developmental-brain-of-rats
#15
Xi Fang, Shiyong Li, Qiang Han, Yilin Zhao, Jie Gao, Jing Yan, Ailin Luo
Nowadays many children receive operations with general anesthesia. Isoflurane is a commonly-used general anesthetic. Numbers of studies demonstrated that isoflurane induced neurotoxicity and neurobehavioral deficiency in young rats, however, the underlying mechanism remained unknown. Cell division cycle 42 (cdc42) played an important role in regulating synaptic vesicle trafficking and actin dynamics in neuron, which closely linked to synaptic plasticity and dendritic spine formation. Meanwhile, cdc42 also involved in many neurodegenerative diseases...
June 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28642117/soluble-epoxide-hydrolase-as-a-therapeutic-target-for-pain-inflammatory-and-neurodegenerative-diseases
#16
REVIEW
Karen M Wagner, Cindy B McReynolds, William K Schmidt, Bruce D Hammock
Eicosanoids are biologically active lipid signaling molecules derived from polyunsaturated fatty acids. Many of the actions of eicosanoid metabolites formed by cyclooxygenase and lipoxygenase enzymes have been characterized, however, the epoxy-fatty acids (EpFAs) formed by cytochrome P450 enzymes are newly described by comparison. The EpFA metabolites modulate a diverse set of physiologic functions that include inflammation and nociception among others. Regulation of EpFAs occurs primarily via release, biosynthesis and enzymatic transformation by the soluble epoxide hydrolase (sEH)...
June 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28641777/role-of-parl-pink1-parkin-pathway-in-adipocyte-differentiation
#17
Ming-Yuh Shiau, Pin-Shen Lee, Ying-Jyun Huang, Ching-Ping Yang, Chiao-Wan Hsiao, Kai-Yun Chang, Huan-Wen Chen, Yih-Hsin Chang
OBJECTIVE: Adipogenesis determines the number of adipocytes which is increased when individuals become obese. Mitochondria undergo remarkable morphological and functional changes during adipogenesis. PTEN-induced kinase 1 (PINK1) is pivotal to maintain mitochondrial homeostasis in neural cells. The present study aimed at investigating effects of PINK1 on adipogenesis and energy metabolism. METHODS: Expression of presenilin associated rhomboid-like protein (PARL), PINK1 and Parkin, as well as the interaction among these proteins was temporally examined during adipogenesis...
July 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28641775/is-toxoplasma-gondii-infection-protective-against-multiple-sclerosis-risk
#18
Asli Koskderelioglu, Ilhan Afsar, Bayram Pektas, Muhtesem Gedizlioglu
BACKGROUND: Parasitic infections may play a protective role in neurodegenative diseases. OBJECTıVE: To determine the association between Toxoplasma gondii (T. gondii) infection and Multiple Sclerosis (MS). METHODS: One hundred fifteen patients with MS were included in the study. Sixty age and gender-matched healthy subjects were recruited as controls. Subjects were assessed for clinical and demographic parameters. The presence of specific IgG antibodies against T...
July 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28641540/metallothionein-is-a-potential-therapeutic-strategy-for-amyotrophic-lateral-sclerosis
#19
Shin-Ichi Ono
Lou Gehrig's disease, a synonym of amyotrophic lateral sclerosis, is an adult-onset lethal neurodegenerative disorder. Irrespective of extensive efforts to elucidate the pathogenesis of the disease and searches for therapies, no favorable pharmacotherapeutic strategies have yet to be proposed. In a popular rodent model of ALS, G93A SOD1 mice, intracellular copper conditions were geared toward copper accumulation inside cells, resulting in an acceleration of oxidative stress and apoptotic process. Disruption of intracellular copper homeostasis was common to transgenic mice expressing human mutant SOD1s...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641510/recent-advances-on-the-role-of-neurogenesis-in-the-adult-brain-therapeutic-potential-in-parkinson-s-and-alzheimer-s-diseases
#20
Khaled Salman Radad, Rudolf Moldzio, Mubarak Al-Shraim, Barbara Kranner, Christopher Krewenka, Wolf-Dieter Rausch
Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus...
June 22, 2017: CNS & Neurological Disorders Drug Targets
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