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Neurodegeratives

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https://www.readbyqxmd.com/read/29464565/ryanodine-receptor-structure-and-function-in-health-and-disease
#1
Gaetano Santulli, Daniel Lewis, Amedee des Georges, Andrew R Marks, Joachim Frank
Ryanodine receptors (RyRs) are ubiquitous intracellular calcium (Ca2+ ) release channels required for the function of many organs including heart and skeletal muscle, synaptic transmission in the brain, pancreatic beta cell function, and vascular tone. In disease, defective function of RyRs due either to stress (hyperadrenergic and/or oxidative overload) or genetic mutations can render the channels leaky to Ca2+ and promote defective disease-causing signals as observed in heat failure, muscular dystrophy, diabetes mellitus, and neurodegerative disease...
2018: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/29196167/cathepsin-b-links-oxidative-stress-to-the-activation-of-nlrp3-inflammasome
#2
Hua Bai, Bo Yang, Wenfeng Yu, Yan Xiao, Dejun Yu, Qifang Zhang
Oxidative stress-mediated activation of NLRP3 inflammasome in microglia is critical in the development of neurodegerative diseases such as Alzheimer's disease (AD), Parkinson disease (PD). However, the mechanism underlying oxidative stress activates NLRP3 inflammasome remains exclusive. Here we demonstrated cathepsin B (CTSB) as a regulator of the activation of NLRP3 inflammasome by H2 O2 ·H2 O2 induced IL-1β secretion in NLRP3 inflammasome-dependent manner·H2 O2 treatment increased CTSB activity, which in turn activated NLRP3 inflammasome, and subsequently processed pro-caspase-1 cleavage into caspase-1, resulting in IL-1 β secretion...
January 1, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29096697/race-modifies-the-relationship-between-cognition-and-alzheimer-s-disease-cerebrospinal-fluid-biomarkers
#3
Jennifer C Howell, Kelly D Watts, Monica W Parker, Junjie Wu, Alexander Kollhoff, Thomas S Wingo, Cornelya D Dorbin, Deqiang Qiu, William T Hu
BACKGROUND: African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD...
November 2, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28987179/genetics-of-neurodegenerative-diseases-an-overview
#4
REVIEW
Lasse Pihlstrøm, Sarah Wiethoff, Henry Houlden
Genetic factors are central to the etiology of neurodegeneration, both as monogenic causes of heritable disease and as modifiers of susceptibility to complex, sporadic disorders. Over the last two decades, the identification of disease genes and risk loci has led to some of the greatest advances in medicine and invaluable insights into pathogenic mechanisms and disease pathways. Large-scale research efforts, novel study designs, and advances in methodology are rapidly expanding our understanding of the genome and the genetic architecture of neurodegenerative disease...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28956342/genetic-understanding-of-stroke-treatment-potential-role-for-phosphodiesterase-inhibitors
#5
REVIEW
Anjana Munshi, Satrupa Das
Phosphodiesterase (PDE) gene family is a large family having at least 21 genes and multiple versions (isoforms) of the phosphodiesterase enzymes. These enzymes catalyze the inactivation of intracellular mediators of signal transduction such as cAMP and cGMP and therefore, play a pivotal role in various cellular functions. PDE inhibitors (PDEI) are drugs that block one or more of the five subtypes of the PDE family and thereby prevent inactivation of the intracellular cAMP and cGMP by the respective PDE-subtypes...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28543935/neurodegeneration-in-ataxia-telangiectasia-multiple-roles-of-atm-kinase-in-cellular-homeostasis
#6
REVIEW
Kay Rui Choy, Dianne J Watters
Ataxia-telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency, and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (ataxia-telangiectasia mutated) gene. ATM is a sensor of DNA double-strand breaks (DSBs) and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signaling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease...
January 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28522732/unbiased-proteomics-of-early-lewy-body-formation-model-implicates-active-microtubule-affinity-regulating-kinases-marks-in-synucleinopathies
#7
Michael X Henderson, Charlotte Hiu-Yan Chung, Dawn M Riddle, Bin Zhang, Ronald J Gathagan, Steven H Seeholzer, John Q Trojanowski, Virginia M Y Lee
Parkinson's disease (PD) patients progressively accumulate intracytoplasmic inclusions formed by misfolded α-synuclein known as Lewy bodies (LBs). LBs also contain other proteins that may or may not be relevant in the disease process. To identify proteins involved early in LB formation, we performed proteomic analysis of insoluble proteins in a primary neuron culture model of α-synuclein pathology. We identified proteins previously found in authentic LBs in PD as well as several novel proteins, including the microtubule affinity-regulating kinase 1 (MARK1), one of the most enriched proteins in this model of LB formation...
June 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28461971/cholesterol-in-the-pathogenesis-of-alzheimer-s-parkinson-s-diseases-and-autism-link-to-synaptic-dysfunction
#8
A M Petrov, M R Kasimov, A L Zefirov
In our previous review, we described brain cholesterol metabolism in control conditions and in the case of some rare neurological pathologies linked to defects in the genes which are directly involved in the synthesis and/or traffic of cholesterol. Here, we have analyzed disruptions in cholesterol homeostasis in widespread neurodegenerative diseases (Alzheimer's and Parkinson's diseases) and autism spectrum disorders. We particularly focused on the synaptic dysfunctions that could arise from changes in both membrane cholesterol availability and oxysterol production...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28424579/grp78-at-the-centre-of-the-stage-in-cancer-and-neuroprotection
#9
REVIEW
Caty Casas
The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is activated after endoplasmic reticulum (ER) stress in the cells. Most of these newly discovered activities depend on its position within the cell. GRP78 is located mainly in the ER, but it has also been observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane, and secreted, although it is dedicated mostly to engage endogenous cytoprotective processes...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28391270/single-retinal-layer-evaluation-in-patients-with-type-1-diabetes-with-no-or-early-signs-of-diabetic-retinopathy-the-first-hint-of-neurovascular-crosstalk-damage-between-neurons-and-capillaries
#10
Fabio Scarinci, Fabiana Picconi, Gianni Virgili, Paola Giorno, Antonio Di Renzo, Monica Varano, Simona Frontoni, Mariacristina Parravano
PURPOSE: To analyze the retinal-choroidal changes in type 1 diabetes mellitus (DM1) patients with no or early signs of diabetic retinopathy (DR). METHODS: Seventy-six eyes of 38 DM1 patients and 26 control eyes were included. Nine individual retinal layer thickness measurements were obtained using the spectral domain-optical coherence tomography automated segmentation algorithm. RESULTS: The retinal nerve fiber layer was slightly thinner in all explored quadrants, even if the reduction was not significant in DM1 eyes versus control eyes...
2017: Ophthalmologica. Journal International D'ophtalmologie
https://www.readbyqxmd.com/read/28363724/hidden-targets-of-ubiquitin-proteasome-system-to-prevent-diabetic-nephropathy
#11
REVIEW
Santosh Kumar Goru, Almesh Kadakol, Anil Bhanudas Gaikwad
Diabetic nephropathy (DN) is the major cause of end stage renal failure. Although, several therapeutic targets have emerged to prevent the progression of DN, the number of people with DN still continues to rise worldwide, suggesting an urgent need of novel targets to prevent DN completely. Currently, the role of ubiquitin proteasome system (UPS) has been highlighted in the pathogenesis and progression of various diseases like obesity, insulin resistance, atherosclerosis, cancers, neurodegerative disorders and including secondary complications of diabetes...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28330956/predictive-markers-for-early-conversion-of-irbd-to-neurodegenerative-synucleinopathy-diseases
#12
Yuanyuan Li, Wenyan Kang, Qiong Yang, Lina Zhang, Linyuan Zhang, Fangyi Dong, Shengdi Chen, Jun Liu
OBJECTIVE: To determine the predictive value of clinical assessment and dopamine transporter (DAT) uptake for the early development of neurodegenerative synucleinopathy diseases from idiopathic REM sleep behavior disorder (iRBD) over 5 years in a Chinese population. METHODS: Forty-three patients with iRBD were administered clinical assessment tests, and 35 were examined by DAT-SPECT imaging during 2011. Cox proportional hazard and Kaplan-Meier analyses were used to evaluate the predictive value of the markers in a follow-up study over 5 years...
April 18, 2017: Neurology
https://www.readbyqxmd.com/read/28048182/su-g-iep1-14-the-relationship-between-voxel-based-morphometry-and-fiber-tract-abnormalities-by-correlation-analysis-in-patients-with-neurodegerative-disease
#13
R Juh, T Suh, J Han, C Kim, C Oh
PURPOSE: We evaluated the relationship between white matter (WM) tract disintegration and gray matter (GM) atrophy in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, using diffusion tensor imaging (DTI) and an optimized voxel-based analysis. METHODS: Two hundred thirty one individuals (61 controls, 116 MCI and 54 AD) were included. Voxel-based WM tract statistics was used to obtain whole-brain maps of WM bundles for FA. Voxel-based morphometry (VBM) was conducted to detect regions of gray matter (GM) atrophy in the AD, MCI group relative to the control group...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28034783/cerebellar-insulin-igf-1-signaling-in-diabetic-rats-effects-of-exercise-training
#14
Mariana Eiras Borges, Alessandra Mussi Ribeiro, José Rodrigo Pauli, Luciana Mendonça Arantes, Eliete Luciano, Leandro Pereira de Moura, José Alexandre Curiacos de Almeida Leme, Alessandra Medeiros, Natália Oliveira Bertolini, Clarice Yoshiko Sibuya, Ricardo José Gomes
The Diabetes Mellitus (DM) is a chronic disease associated with loss of brain regions such as the cerebellum, increasing the risk of developing neurodegenerative diseases such as Parkinson's disease (PD). In the brain of diabetic and PD organisms the insulin/IGF-1 signaling is altered. Exercise training is an effective intervention for the prevention of neurodegerative diseases since it release neurotrophic factors and regulating insulin/IGF-1 signaling in the brain. This study aimed to evaluate the proteins involved in the insulin/IGF-1 pathway in the cerebellum of diabetic rats subjected to exercise training protocol...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27984051/brain-endothelial-dysfunction-following-pyrithiamine-induced-thiamine-deficiency-in-the-rat
#15
Sumit Sarkar, Serguei Liachenko, Merle G Paule, John Bowyer, Joseph P Hanig
Prolonged vitamin B1 (thiamine) deficiency can lead to neurological disorders such as Wernicke's encephalopathy and Wernicke-Korsakoff Syndrome (WKS) in humans. These thiamine deficiency disorders have been attributed to vascular leakage, blood-brain barrier breakdown and neuronal loss in the diencephalon and brain stem. However, endothelial dysfunction following thiamine deficiency and its relationship to the phenomenon of neurodegeneration has not been clearly elucidated. The present study sought to begin to address this issue by evaluating vascular morphology and integrity in a pyrithiamine (PT)-induced rat model of thiamine deficiency...
December 2016: Neurotoxicology
https://www.readbyqxmd.com/read/27927065/aqueous-extract-of-securidaca-longipendunculata-oliv-and-olax-subscropioidea-inhibits-key-enzymes-acetylcholinesterase-and-butyrylcholinesterase-linked-with-alzheimer-s-disease-in-vitro
#16
COMPARATIVE STUDY
Jamiu A Saliu, Ayodeji A Olabiyi
CONTEXT: Plants have historically been used to treat neurodegerative diseases which include Alzheimer's disease. OBJECTIVE: This study investigated the antioxidant properties and inhibitory effect of aqueous extracts of Securidaca longipendunculata root and Olax subscropioidea leaf on the cholinergic system in rat brain in vitro. MATERIALS AND METHODS: Aqueous extracts (1:20 w/v) of S. longipendunculata root and O. subscropioidea leaf was prepared and the ability of the extract to inhibit the activities of acetylcholinesterase and butyrylcholinesterase was evaluated as well as antioxidants as typified by 2,2-azino-bis-(3-ethylbenthiazoline-6-sulphonic acid (ABTS(•)) radical scavenging ability and Fe chelation spectophotometrically...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27591175/who-watches-the-watchmen-regulation-of-the-expression-and-activity-of-sirtuins
#17
REVIEW
Marcin Buler, Ulf Andersson, Jukka Hakkola
Sirtuins (SIRT1-7) are a family of nicotine adenine dinucleotide (NAD+ )-dependent enzymes that catalyze post-translational modifications of proteins. Together, they regulate crucial cellular functions and are traditionally associated with aging and longevity. Dysregulation of sirtuins plays an important role in major diseases, including cancer and metabolic, cardiac, and neurodegerative diseases. They are extensively regulated in response to a wide range of stimuli, including nutritional and metabolic challenges, inflammatory signals or hypoxic and oxidative stress...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27486795/transcranial-sonography-of-the-insula-digitized-image-analysis-of-fusion-images-with-magnetic-resonance
#18
D Školoudík, P Bártová, J Mašková, P Dušek, J Blahuta, K Langová, U Walter, R Herzig
Purpose: Transcranial B-mode sonography (TCS) of brain parenchyma is increasingly used as a diagnostic tool for movement disorders. Accordingly, experimental B-Mode Assist software was developed to enable digitized analysis of the echogenicity of predefined brain regions. The aim of the study was to assess the reproducibility of digitized TCS image analysis of the insula. Materials and Methods: A total of 130 patients with an indication for neurosonological examination were screened for participation in the study...
December 2016: Ultraschall in der Medizin
https://www.readbyqxmd.com/read/25308265/homogeneous-bioluminescent-proteasome-assays
#19
Martha A O'Brien, Richard A Moravec, Terry L Riss, Robert F Bulleit
Protein degradation is mediated predominantly through the ubiquitin-proteasome pathway. The importance of the proteasome in regulating degradation of proteins involved in cell-cycle control, apoptosis, and angiogenesis led to the recognition of the proteasome as a therapeutic target for cancer. The proteasome is also essential for degrading misfolded and aberrant proteins, and impaired proteasome function has been implicated in neurodegerative and cardiovascular diseases. Robust, sensitive assays are essential for monitoring proteasome activity and for developing inhibitors of the proteasome...
2015: Methods in Molecular Biology
https://www.readbyqxmd.com/read/25076225/gabapentin-enhances-neurogenesis-in-e14-rat-embryonic-neocortex-stem-cells
#20
B Paknejad, A Kebriaeezadeh, M H Ghahremani, M Gharghabi, S N Ostad
Many anticonvulsant drugs have been studied for their non conventional therapeutic effects on neurodegerative diseases but merely a few demonstrated potential neurogenic characteristic. Gabapentin as a well-known mood stabilizer was studied for its potential capability to promote neurogenesis in embryonic rat cortical stem cells. Rat E14 cortical stem cells were exposed to gabapentin during differentiation for 7 days and subjected to immunocytochemistry. The phenotypic changes were evaluated in the ultimately survived and differentiated cells...
August 2015: Drug Research
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