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Neurodegenerative diseases

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https://www.readbyqxmd.com/read/29149763/formulation-and-anti-neurotoxic-activity-of-baicalein-incorporating-neutral-nanoliposome
#1
Farhang Aliakbari, Ali Akbar Shabani, Hassan Bardania, Hossein Mohammad-Beigi, Amir Tayaranian Marvian, Faezeh Dehghani Esmatabad, Abbas Ali Vafaei, Seyed Abbas Shojaosadati, Ali Akbar Saboury, Gunna Christiansen, Daniel E Otzen, Dina Morshedi
Despite extensive studies of the effects of herbal-derived small molecules in the biopharmaceutical and biomedical sciences, their low solubility and stability remain a challenge. Here we focus on baicalein, a small molecule showing potential against neurodegenerative diseases such as Parkinson's and Alzheimer's. However, therapeutic usage in vivo is challenged by low solubility and stability. To address this we have applied neutrally-charged nanoliposome (NLP) as carrier for baicalein. Baicalein was incorporated into NLP to form NLP-Ba at molar baicalain:lipid ratios of up to 1:3, giving a drug entrapment efficiency of 96...
November 11, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29149615/rethinking-unconventional-translation-in-neurodegeneration
#2
REVIEW
Fen-Biao Gao, Joel D Richter, Don W Cleveland
Eukaryotic translation is tightly regulated to ensure that protein production occurs at the right time and place. Recent studies on abnormal repeat proteins, especially in age-dependent neurodegenerative diseases caused by nucleotide repeat expansion, have highlighted or identified two forms of unconventional translation initiation: usage of AUG-like sites (near cognates) or repeat-associated non-AUG (RAN) translation. We discuss how repeat proteins may differ due to not just unconventional initiation, but also ribosomal frameshifting and/or imperfect repeat DNA replication, expansion, and repair, and we highlight how research on translation of repeats may uncover insights into the biology of translation and its contribution to disease...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29149385/pre-clinical-models-in-pediatric-traumatic-brain-injury-challenges-and-lessons-learned
#3
REVIEW
Patrick M Kochanek, Jessica S Wallisch, Hülya Bayır, Robert S B Clark
PURPOSE: Despite the enormity of the problem and the lack of new therapies, research in the pre-clinical arena specifically using pediatric traumatic brain injury (TBI) models is limited. In this review, some of the key models addressing both the age spectrum of pediatric TBI and its unique injury mechanisms will be highlighted. Four topics will be addressed, namely, (1) unique facets of the developing brain important to TBI model development, (2) a description of some of the most commonly used pre-clinical models of severe pediatric TBI including work in both rodents and large animals, (3) a description of the pediatric models of mild TBI and repetitive mild TBI that are relatively new, and finally (4) a discussion of challenges, gaps, and potential future directions to further advance work in pediatric TBI models...
October 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29149165/-reflections-on-the-death-of-my-father
#4
Domenico Ribatti
This short essay aims to provide the reader with some general considerations from a private matter, namely the death of the author's father after a long and disabling neurodegenerative disease. The author's reflection revolves around the meaning of death, the relationship between children and parents, the importance of individual and collective memory, and the role that physicians should have in dealing with relatives of subjects suffering from this type of disease.
November 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/29149058/neurotrophic-and-neuroregenerative-effects-of-gh-igf1
#5
Vittorio Emanuele Bianchi, Vittorio Locatelli, Laura Rizzi
INTRODUCTION: Human neurodegenerative diseases increase progressively with age and present a high social and economic burden. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are both growth factors exerting trophic effects on neuronal regeneration in the central nervous system (CNS) and peripheral nervous system (PNS). GH and IGF-1 stimulate protein synthesis in neurons, glia, oligodendrocytes, and Schwann cells, and favor neuronal survival, inhibiting apoptosis. This study aims to evaluate the effect of GH and IGF-1 on neurons, and their possible therapeutic clinical applications on neuron regeneration in human subjects...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29149024/the-role-of-the-mammalian-prion-protein-in-the-control-of-sleep
#6
REVIEW
Amber Roguski, Andrew C Gill
Sleep disruption is a prevalent clinical feature in many neurodegenerative disorders, including human prion diseases where it can be the defining dysfunction, as in the case of the "eponymous" fatal familial insomnia, or an early-stage symptom as in certain types of Creutzfeldt-Jakob disease. It is important to establish the role of the cellular prion protein (PrP(C)), the key molecule involved in prion pathogenesis, within the sleep-wake system in order to understand fully the mechanisms underlying its contribution to both healthy circadian rhythmicity and sleep dysfunction during disease...
November 17, 2017: Pathogens
https://www.readbyqxmd.com/read/29148236/emerging-roles-of-er-stress-in-the-aetiology-and-pathogenesis-of-alzheimer-s-disease
#7
REVIEW
Yannis Gerakis, Claudio Hetz
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synaptic dysfunction and accumulation of abnormal aggregates formed by amyloid-β peptides or phophorylated Tau proteins. Accumulating evidence suggests that alterations in the buffering capacity of the proteostasis network is a salient feature of AD. The endoplasmic reticulum (ER) is the main compartment involved in protein folding and secretion and is drastically affected in AD neurons. ER stress triggers the activation of the Unfolded Protein Response (UPR), a signal transduction pathway that enforces adaptive programs to recover homeostasis or trigger apoptosis of irreversibly damaged cells...
November 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29148035/late-age-onset-of-amyotrophic-lateral-sclerosis-is-often-not-considered-in-elderly-people
#8
E Broussalis, S Grinzinger, A B Kunz, M Killer-Oberpfalzer, E Haschke-Becher, H-P Hartung, J Kraus
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing an upper and lower motor neuron loss. It is neurology textbook knowledge that the mean age of onset is about 60 years. However, recent investigations show an increasing incidence in older persons. We therefore evaluated whether ALS is potentially not considered in elderly people with ALS symptoms, respectively, not recognized. MATERIALS AND METHODS: We included retrospectively all patients with ALS diagnoses after work-up that were admitted to our neurological and geriatric departments from 2007 to 2010 and collected their clinical data...
November 17, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/29148034/role-of-p62-sqstm1-beyond-autophagy-a-lesson-learned-from-drug-induced-toxicity-in-vitro
#9
Fernando Alegre, Ángela B Moragrega, Miriam Polo, Alberto Marti-Rodrigo, Juan V Esplugues, Ana Blas-Garcia, Nadezda Apostolova
BACKGROUND AND PURPOSE: SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Alterations in its function have been associated with a long list of human pathologies such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood...
November 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29147910/therapeutic-activities-of-dj-1-and-its-binding-compounds-against-neurodegenerative-diseases
#10
Masatoshi Inden, Daijiro Yanagisawa, Masanori Hijioka, Hiroyoshi Ariga, Yoshihisa Kitamura
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Loss-of-function mutations in the gene encoding PARK7/DJ-1 were identified in familial PD. Wild-type DJ-1 acts as an oxidative stress sensor in neural cells. Previously, we identified binding compounds of DJ-1, including UCP0045037/compound A, UCP0054278/compound B, and compound-23 (comp-23), by in silico virtual screening. These compounds prevented oxidative stress-induced dopaminergic neuronal death and restored locomotion defects in animal models of PD...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147908/dj-1-as-a-biomarker-of-parkinson-s-disease
#11
Yoshiro Saito
Parkinson's disease is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1 has been identified as a causative gene of a familial form of Parkinson's disease, PARK7, and plays a significant role in antioxidative defense, protecting cells from oxidative stress. A cysteine residue of DJ-1 at position 106 (Cys-106) is preferentially oxidized under oxidative stress. This reactive Cys-106 plays a critical role in the biological function of DJ-1, which could act as a sensor of oxidative stress by regulating antioxidative defense depending on Cys-106 oxidation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147904/the-multifaceted-roles-of-dj-1-as-an-antioxidant
#12
Prahlad V Raninga, Giovanna Di Trapani, Kathryn F Tonissen
The DJ-1 protein was originally linked with Parkinson's disease and is now known to have antioxidant functions. The protein has three redox-sensitive cysteine residues, which are involved in its dimerisation and functional properties. A mildly oxidised form of DJ-1 is the most active form and protects cells from oxidative stress conditions. DJ-1 functions as an antioxidant through a variety of mechanisms, including a weak direct antioxidant activity by scavenging reactive oxygen species. DJ-1 also regulates a number of signalling pathways, including the inhibition of apoptosis signal-regulating kinase 1 (ASK1)-induced apoptosis under oxidative stress conditions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147901/expression-of-dj-1-in-neurodegenerative-disorders
#13
Daria Antipova, Rina Bandopadhyay
In 2003, autosomal recessive loss-of-function mutations were identified in PARK7 gene that caused early-onset Parkinson's disease (PD). The PARK7 gene encodes a conserved protein termed DJ-1. DJ-1 is a ubiquitous protein, and within the brain, it is present in the nucleus and cytoplasm of both neuronal and glial cells. DJ-1 is a multifunctional protein, and numerous studies have ascribed various roles, including antioxidative properties, chaperone function, protease activities, mitochondrial functions and regulation of transcription to the protein...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147899/introduction-overview
#14
Hiroyoshi Ariga, Sanae M M Iguchi-Ariga
The DJ-1 gene is an oncogene and also causative gene for a familial form of Parkinson disease. Although exits of cancer and neurodegenerative diseases, including Parkinson disease, are completely opposite, there are some common points of view between both diseases, including growth and death signaling pathways, and oxidative stresses affect the onset and pathogenesis of both cancer and neurodegenerative diseases. DJ-1 has versatile functions and plays a role in protection against oxidative stress. Inactivation and/or excess activation of DJ-1 functions, therefore, leads to onsets of oxidative stress-related diseases such as type 2 diabetes and male infertility in addition to cancer and neurodegenerative diseases, and studies about DJ-1 will give rise to the common mechanism among these diseases...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147836/effects-of-saffron%C3%A2-and-its-constituents-%C3%A2-crocin-1-crocin-2-and-crocetin-on-%C3%AE-synuclein-fibrils
#15
Eiji Inoue, Yasuharu Shimizu, Ryo Masui, Tomomi Hayakawa, Tomoe Tsubonoya, Satoko Hori, Keiichi Sudoh
Saffron, the stigma of Crocus sativus Linné (Iridaceae family), has been known to inhibit aggregation of β-amyloid, a nerve tissue protein. α-Synuclein (αS) is a 140-amino acid protein found abundantly in various regions of the brain. Its abnormal aggregation and accumulation in nerve tissue are said to cause neurodegenerative diseases such as Parkinson's disease, Lewy body dementia, and multiple-system atrophy. This study (part of this study was presented at the 137th Annual Meeting of the Pharmaceutical Society of Japan) examined the effects of saffron, its constituents (crocin-1, crocin-2, crocetin, and safranal), and crocetin structural analogs (hexadecanedioic acid, norbixin, and trans, trans-muconic acid) on αS aggregation, and αS fibril dissociation...
November 17, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29146293/andrographolide-a-promising-therapeutic-agent-negatively-regulates-glial-cell-derived-neurodegeneration-of-prefrontal-cortex-hippocampus-and-working-memory-impairment
#16
Sudeshna Das, K P Mishra, Lilly Ganju, S B Singh
Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region...
November 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29146111/microrna-expression-patterns-in-human-anterior-cingulate-and-motor-cortex-a-study-of-dementia-with-lewy-bodies-cases-and-controls
#17
Peter T Nelson, Wang-Xia Wang, Sarah A Janse, Katherine L Thompson
OVERVIEW: MicroRNAs (miRNAs) have been implicated in neurodegenerative diseases including Parkinson's disease and Alzheimer's disease (AD). Here, we evaluated the expression of miRNAs in anterior cingulate (AC; Brodmann area [BA] 24) and primary motor (MO; BA 4) cortical tissue from aged human brains in the University of Kentucky AD Center autopsy cohort, with a focus on dementia with Lewy bodies (DLB). METHODS: RNA was isolated from gray matter of brain samples with pathology-defined DLB, AD, AD+DLB, and low-pathology controls, with n=52 cases initially included (n=23 with DLB), all with low (<4hrs) postmortem intervals...
November 13, 2017: Brain Research
https://www.readbyqxmd.com/read/29145874/peripheral-immune-tolerance-alleviates-the-intracranial-lipopolysaccharide-injection-induced-neuroinflammation-and-protects-the-dopaminergic-neurons-from-neuroinflammation-related-neurotoxicity
#18
Yang Liu, Xin Xie, Li-Ping Xia, Hong Lv, Fan Lou, Yan Ren, Zhi-Yi He, Xiao-Guang Luo
BACKGROUND: Neuroinflammation plays a critical role in the onset and development of neurodegeneration disorders such as Parkinson's disease. The immune activities of the central nervous system are profoundly affected by peripheral immune activities. Immune tolerance refers to the unresponsiveness of the immune system to continuous or repeated stimulation to avoid excessive inflammation and unnecessary by-stander injury in the face of continuous antigen threat. It has been proved that the immune tolerance could suppress the development of various peripheral inflammation-related diseases...
November 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29145658/characterization-of-detergent-insoluble-proteome-in-chronic-traumatic-encephalopathy
#19
Jonathan D Cherry, Ahmad Zeineddin, Eric B Dammer, James A Webster, Duc Duong, Nicholas T Seyfried, Allan I Levey, Victor E Alvarez, Bertrand R Huber, Thor D Stein, Patrick T Kiernan, Ann C McKee, James J Lah, Chadwick M Hales
Quantitative proteomics of postmortem human brain can identify dysfunctional proteins that contribute to neurodegenerative disorders like Alzheimer disease (AD) and frontotemporal dementia. Similar studies in chronic traumatic encephalopathy (CTE) are limited, therefore we hypothesized that proteomic sequencing of CTE frontal cortex brain homogenates from varying CTE pathologic stages may provide important new insights into this disorder. Quantitative proteomics of control, CTE and AD brains was performed to characterize differentially expressed proteins, and we identified over 4000 proteins in CTE brains, including significant enrichment of the microtubule associated protein tau...
November 14, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29145208/curcumin-delays-retinal-degeneration-by-regulating-microglia-activation-in-the-retina-of-rd1-mice
#20
Yanhe Wang, Zhiyuan Yin, Lixiong Gao, Dayu Sun, Xisu Hu, Langyue Xue, Jiaman Dai, YuXiao Zeng, Siyu Chen, Boju Pan, Min Chen, Jing Xie, Haiwei Xu
BACKGROUND/AIMS: Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. METHODS: Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice...
November 17, 2017: Cellular Physiology and Biochemistry
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