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Neurodegenerative disease

Bartosz Nizynski, Hanna Nieznanska, Robert Dec, Solomiia Boyko, Wojciech Dzwolak, Krzysztof Nieznanski
Amyloid aggregates of Tau protein have been implicated in etiology of many neurodegenerative disorders including Alzheimer's disease (AD). When amyloid growth is induced by seeding with preformed fibrils assembled from the same protein, structural characteristics of the seed are usually imprinted in daughter generations of fibrils. This so-called conformational memory effect may be compromised when the seeding involves proteins with non-identical sequences leading to the emergence of distinct structural variants of fibrils (amyloid 'strains')...
2018: PloS One
Malbor Asllani, Paul Expert, Timoteo Carletti
Many collective phenomena in Nature emerge from the -partial- synchronisation of the units comprising a system. In the case of the brain, this self-organised process allows groups of neurons to fire in highly intricate partially synchronised patterns and eventually lead to high level cognitive outputs and control over the human body. However, when the synchronisation patterns are altered and hypersynchronisation occurs, undesirable effects can occur. This is particularly striking and well documented in the case of epileptic seizures and tremors in neurodegenerative diseases such as Parkinson's disease...
July 19, 2018: PLoS Computational Biology
Achut Prasad Silwal, H Peter Lu
Dopamine (DA) is the catecholamine neurotransmitter which interacts with dopamine receptors (DARs) to generate dopaminergic signals in nervous system. Dopamine transporter (DAT) interacts with DA to maintain DA's homeostasis in synaptic and perisynaptic space. DAT and DARs have great importance in central nervous system (CNS) since they are associated to the targeted binding of drugs. Interactions of DA, or its analogue with DARs, or DAT have been studied extensively to understand the mechanism of the dopaminergic signaling process and several neurodegenerative diseases including schizophrenia, Parkinson's diseases, addiction, attention deficit hyperactivity disorder (ADHD), and bipolar disorder...
July 19, 2018: ACS Chemical Neuroscience
Xiuqin Jia, Lin Shi, Tianyi Qian, Ying Li, Defeng Wang, Peipeng Liang, Kuncheng Li
OBJECTIVE: This study aimed to test the hypothesis that the statistical Chinese brain template would be more effective to detect gray matter (GM) changes in patients with Alzheimer disease (AD) in Chinese populations. MATERIALS AND METHODS: In total, 50 patients with AD and 50 sex-matched and age-matched healthy controls were included in this study. Chinese2020, a typical statistical Chinese brain template, and MNI152, a typical Caucasian template were used for spatial normalization respectively...
July 17, 2018: Alzheimer Disease and Associated Disorders
David Blum, Yijuang Chern, Maria Rosaria Domenici, Luc Buée, Chien-Yu Lin, William Rea, Sergi Ferré, Patrizia Popoli
Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a mutation in the IT15 gene that encodes for the huntingtin protein. Mutated hungtingtin, although widely expressed in the brain, predominantly affects striato-pallidal neurons, particularly enriched with adenosine A2A receptors (A2A R), suggesting a possible involvement of adenosine and A2A R is the pathogenesis of HD. In fact, polymorphic variation in the ADORA2A gene influences the age at onset in HD, and A2A R dynamics is altered by mutated huntingtin...
June 1, 2018: Journal of caffeine and adenosine research
Angelina Angelova, Markus Drechsler, Vasil M Garamus, Borislav Angelov
Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are bioactive lipids with considerable impact in medicine and nutrition. These compounds exert structuring effects on the cellular membrane organization, regulate the gene expression, and modulate various signaling cascades and metabolic processes. The purpose of the present work is to demonstrate the structural features of ω-3 PUFA-containing three-dimensional supramolecular lipid assemblies suitable for pharmaceutical applications that require soft porous carriers...
March 31, 2018: ACS Omega
José A Morales-Garcia, Irene G Salado, Marina Sanz-San Cristobal, Carmen Gil, Ana Pérez-Castillo, Ana Martínez, Daniel I Pérez
Parkinson's disease (PD), an age-related neurodegenerative disorder that results from a progressive loss of dopaminergic neurons has an enormous economical and human cost. Unfortunately, only symptomatic treatment such as dopamine replacement therapy is available. Therefore, drugs with new mechanisms of action able to protect against neuronal cell death are an urgent need. We here report the in vivo efficacy on dopaminergic neuronal protection in a PD mouse model and the lack of toxicity in zebrafish and Ames test of benzothiazole-based casein kinase-1δ (CK-1δ) nanomolar inhibitors...
August 31, 2017: ACS Omega
Patrick L Donabedian, Mallory Evanoff, Florencia A Monge, David G Whitten, Eva Y Chi
Developing new molecular ligands for the direct detection and tracking of amyloid protein aggregates is key to understanding and defeating myriad neurodegenerative and other disorders including Alzheimer's and Parkinson's diseases. A crucial factor in the performance of an amyloid dye is its ability to detect the amyloid structural motif independent of the sequence of the amyloid-forming protomer. The current study investigates structure-function relationships of a class of novel phenyleneethynylene (PPE)-based dyes and fluorescent polymers using amyloid fibrils formed by two model proteins: lysozyme and insulin...
July 31, 2017: ACS Omega
Francisco J Amaro-Gahete, Alejandro De-la-O, Lucas Jurado-Fasoli, Andrea Espuch-Oliver, Lidia Robles-Gonzalez, Ginés Navarro-Lomas, Tomás de Haro, Pedro Femia, Manuel J Castillo, Angel Gutierrez
Aims: The secreted form of the α-Klotho gene (S-Klotho), which is considered a powerful biomarker of longevity, makes it an attractive target as an anti-ageing therapy against functional decline, sarcopenic obesity, metabolic and cardiovascular diseases, osteoporosis, and neurodegenerative disorders. The S-Klotho plasma levels could be related to physical exercise inasmuch physical exercise is involved in physiological pathways that regulate the S-Klotho plasma levels. FIT-AGEING will determine the effect of different training modalities on the S-Klotho plasma levels (primary outcome) in sedentary healthy adults...
September 2018: Contemporary Clinical Trials Communications
Ji Min Lee, Jungwan Hong, Gyeong Joon Moon, Un Ju Jung, So-Yoon Won, Sang Ryong Kim
An abnormal reorganization of the dentate gyrus and neurotoxic events are important phenotypes in the hippocampus of patients with temporal lobe epilepsy (TLE). The effects of morin, a bioflavonoid constituent of many herbs and fruits, on epileptic seizures have not yet been elucidated, though its beneficial effects, such as its anti-inflammatory and neuroprotective properties, are well-described in various neurodegenerative diseases. In the present study, we investigated whether treatment with morin hydrate (MH) can reduce the susceptibility to seizures, granule cell dispersion (GCD), mammalian target of rapamycin complex 1 (mTORC1) activity, and the increases in the levels of apoptotic molecules and inflammatory cytokines in the kainic acid (KA)-induced seizure mouse model...
June 2018: Experimental Neurobiology
Hyungju Park
Deficient BDNF signaling is known to be involved in neurodegenerative diseases such as Huntington's disease (HD). Mutant huntingtin (mhtt)-mediated disruption of either BDNF transcription or transport is thought to be a factor contributing to striatal atrophy in the HD brain. Whether and how activity-dependent BDNF secretion is affected by the mhtt remains unclear. In the present study, I provide evidence for differential effects of the mhtt on cortical BDNF secretion in the striatum during HD progression. By two-photon imaging of fluorescent BDNF sensor (BDNF-pHluorin and -EGFP) in acute striatal slices of HD knock-in model mice, I found deficient cortical BDNF secretion regardless of the HD onset, but antisense oligonucleotide (ASO)-mediated reduction of htts only rescues BDNF secretion in the early HD brain before the disease onset...
June 2018: Experimental Neurobiology
Ankit Parikh, Krishna Kathawala, Jintao Li, Chi Chen, Zhengnan Shan, Xia Cao, Yan-Jiang Wang, Sanjay Garg, Xin-Fu Zhou
Background: Alzheimer's disease (AD) is a devastating neurodegenerative disorder that lacks any disease-modifying drug for the prevention and treatment. Edaravone (EDR), an approved free radical scavenger, has proven to have potential against AD by targeting multiple key pathologies including amyloid-beta (Aβ), tau phosphorylation, oxidative stress, and neuroinflammation. To enable its oral use, novel edaravone formulation (NEF) was previously developed. The aim of the present investigation was to evaluate safety and efficacy of NEF by using in vitro/in vivo disease model...
2018: Drug Design, Development and Therapy
Marie-Pier Girouard, Mardja Bueno, Victoria Julian, Sienna Drake, Alexandra B Byrne, Alyson E Fournier
Neurons face a series of morphological and molecular changes following trauma and in the progression of neurodegenerative disease. In neurons capable of mounting a spontaneous regenerative response, including invertebrate neurons and mammalian neurons of the peripheral nervous system (PNS), axons regenerate from the proximal side of the injury and degenerate on the distal side. Studies of Wallerian degeneration slow (WldS /Ola) mice have revealed that a level of coordination between the processes of axon regeneration and degeneration occurs during successful repair...
July 18, 2018: Developmental Neurobiology
Katerina Christofides, Resmi Menon, Christopher E Jones
The prevalence of metal dysregulation in many neurodegenerative and neurocognitive disorders has compelled many studying such diseases to investigate the mechanisms underlying metal regulation in the central nervous system. Metal homoeostasis is often complex, with sophisticated, multilayered pathways in operation. G protein-coupled receptors are omnipresent on cell membranes and have intriguing mechanisms of endocytosis and trafficking that may be useful in metal homoeostasis. Indeed, many receptors and/or their cognate ligands are able to bind metals, and in many cases metals are considered to have neuromodulatory roles as a result of receptor binding...
July 18, 2018: Cell Biochemistry and Biophysics
Gabriela O Bodea, Eleanor G Z McKelvey, Geoffrey J Faulkner
Over the past decade, major discoveries in retrotransposon biology have depicted the neural genome as a dynamic structure during life. In particular, the retrotransposon LINE-1 (L1) has been shown to be transcribed and mobilized in the brain. Retrotransposition in the developing brain, as well as during adult neurogenesis, provides a milieu in which neural diversity can arise. Dysregulation of retrotransposon activity may also contribute to neurological disease. Here, we review recent reports of retrotransposon activity in the brain, and discuss the temporal nature of retrotransposition and its regulation in neural cells in response to stimuli...
July 2018: Open Biology
Simon Hsu, Brian A Gordon, Russ Hornbeck, Joanne B Norton, Denise Levitch, Adia Louden, Ellen Ziegemeier, Robert Laforce, Jasmeer Chhatwal, Gregory S Day, Eric McDade, John C Morris, Anne M Fagan, Tammie L S Benzinger, Alison M Goate, Carlos Cruchaga, Randall J Bateman, Celeste M Karch
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. Mutations in amyloid-β precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the pathogenic cause of autosomal dominant AD (ADAD). However, polymorphisms also exist within these genes. METHODS: In order to distinguish polymorphisms from pathogenic mutations, the DIAN Expanded Registry has implemented an algorithm for determining ADAD pathogenicity using available information from multiple domains, including genetic, bioinformatic, clinical, imaging, and biofluid measures and in vitro analyses...
July 18, 2018: Alzheimer's Research & Therapy
Irene Håkansson, Anders Tisell, Petra Cassel, Kaj Blennow, Henrik Zetterberg, Peter Lundberg, Charlotte Dahle, Magnus Vrethem, Jan Ernerudh
BACKGROUND: There is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and other biomarkers, subsequent disease activity, and brain volume loss in CIS and RRMS. METHODS: A panel of neurodegenerative and neuroinflammatory markers were analyzed in repeated CSF samples from 41 patients with CIS or RRMS in a prospective longitudinal cohort study and from 22 healthy controls...
July 18, 2018: Journal of Neuroinflammation
Samuel Suarez-Mendez, Carlos Alfonso Tovilla-Zárate, Isela E Juárez-Rojop, Deysi Y Bermúdez-Ocaña
Erythropoietin (EPO) is required for promoting the progress of erythroid differentiation. However, the discovery of EPO and the EPO receptor (EPOR) in the nervous system may contribute to new treatment strategies for the use of EPO in neurodegenerative disorders. Diabetic neuropathy is a neurodegenerative disease that affects a large proportion of diabetic patients and results in alterations in functionality, mood and sleep. The pathogenic mechanisms generating diabetic neuropathy involve: Schwannopathy, polyol pathway activity, advanced glycation end-products (AGEs) accumulation, protein kinase C (PKC) activity, increased hexosamine pathway flux, oxidative stress, nitric oxide and inflammation...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ravi Chandra Sekhara Reddy Danduga, Subba Reddy Dondapati, Phani Kumar Kola, Lilly Grace, Rahil Vandana Bisky Tadigiri, Vijaya Kishore Kanakaraju
Huntington's disease (HD) is an autosomal neurodegenerative disease characterized by chorea, dystonia, motor ataxia, cognitive decline and psychiatric disorders with gradual loss of nerve cells and has no existing cure for the disease. In the present study, a mitochondrial toxin, 3-nitropropionic acid (3-NP) is used to induce HD like symptoms in rats. Tetramethylpyrazine is one of the active ingredients of Chuan Xiong which was reported to have neurotrophic and neuroprotective activities. The present study was designed to evaluate the role of TMP on 3-NP induced behavioral, biochemical, neurochemical, and histological alterations in the different regions of the brain...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Martin L Brady, Raghu Raghavan, Jaime Mata, Mike Wilson, Scott Wilson, Rick M Odland, William C Broaddus
BACKGROUND/AIMS: "Whole-brain" infusions have emerged as a potential need with the promise of disease-modifying therapies for neurodegenerative diseases. In addition, several current clinical trials in brain cancer utilize direct delivery of drugs that are required to fill large volumes. Such requirements may not be well served by conventional single port catheters with their "point source" of delivery. Our aim is to examine infusions into large volumes of heterogeneous tissue, aiming for uniformity of distribution...
July 18, 2018: Stereotactic and Functional Neurosurgery
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