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https://www.readbyqxmd.com/read/28816645/a-systems-model-of-parkinson-s-disease-using-biochemical-systems-theory
#1
Hemalatha Sasidharakurup, Nidheesh Melethadathil, Bipin Nair, Shyam Diwakar
Parkinson's disease (PD), a neurodegenerative disorder, affects millions of people and has gained attention because of its clinical roles affecting behaviors related to motor and nonmotor symptoms. Although studies on PD from various aspects are becoming popular, few rely on predictive systems modeling approaches. Using Biochemical Systems Theory (BST), this article attempts to model and characterize dopaminergic cell death and understand pathophysiology of progression of PD. PD pathways were modeled using stochastic differential equations incorporating law of mass action, and initial concentrations for the modeled proteins were obtained from literature...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28807575/triple-reuptake-inhibitors-design-synthesis-and-structure-activity-relationship-of-benzylpiperidine-tetrazoles
#2
Suresh Paudel, Xiao Min, Srijan Acharya, Daulat Bikram Khadka, Goo Yoon, Kyeong-Man Kim, Seung Hoon Cheon
Monoamine transporters are important targets in the treatment of various central nervous disorders. Several limitations of traditional reuptake inhibitors, like delayed onset of action, insomnia, and sexual dysfunction, have compelled the search for safer, more effective compounds. In this study, we have sought to identify novel monoamine reuptake inhibitors. Based upon the docking study of compounds that we had reported previously, aromatic rings (A1) were modified to generate a novel series of benzylpiperidine-tetrazoles...
July 27, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28805572/personalized-medicine-and-nonmotor-symptoms-in-parkinson-s-disease
#3
Nataliya Titova, K Ray Chaudhuri
Parkinson's disease (PD) is a multineurotransmitter dysfunction related disorder resulting in a range of motor and nonmotor symptoms. Phenotypic heterogeneity is pronounced in PD and nonmotor symptoms dominant subtypes have been described. These endophenotypes may be underpinned by considerable nondopaminergic dysfunction; however, conventional treatment of PD continues to be mostly reliant on dopamine replacement strategy or manipulation of brain dopaminergic pathways. Consequently, treatment of many nondopaminergic nonmotor and some motor symptoms remains a key unmet need...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805144/a-qm-protein-ligand-investigation-of-anti-psychotic-drugs-with-the-dopamine-d2-receptor-d2r
#4
Ramin Ekhteiari Salmas, Yusuf Serhat Is, Serdar Durdagi, Matthias Stein, Mine Yurtsever
The dopamine D2 Receptor (D2R) is a member of the G-Protein Coupled Receptor (GPCR) family and plays a critical role in neurotransmission activities in the human brain. Dysfunction in dopamine receptor signaling may lead to mental health illnesses such as schizophrenia and Parkinson's disease. D2R is the target protein of the commonly used anti-psychotic drugs such as risperidone, clozapine, aripiprazole, olanzapine, ziprasidone and quetiapine. Due to their significant side effects and nonselective profiles, the discovery of novel drugs has become a challenge for researchers working in this field...
August 14, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28802933/cognition-in-parkinson-s-disease
#5
Claire O'Callaghan, Simon J G Lewis
Cognitive decline is now recognized as a common nonmotor symptom of Parkinson's disease, and it has been the subject of increasing research in recent decades. Cognitive deficits in Parkinson's disease can be distinguished as dopaminergically mediated executive dysfunction seen in the milder stages vs a global dementia syndrome that can occur with disease progression. The neural basis of these deficits has been explored from the perspective of multimodal imaging techniques to measure the structural, functional, and metabolic correlates of cognitive decline in Parkinson's disease...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28802926/nonmotor-symptoms-and-natural-history-of-parkinson-s-disease-evidence-from-cognitive-dysfunction-and-role-of-noninvasive-interventions
#6
Roberta Biundo, Eleonora Fiorenzato, Angelo Antonini
Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor and nonmotor symptoms (NMS). Several subsequent studies substantiate the great functional burden related to NMS, their progression, and negative effect on quality of life in PD. Additional evidence indicates interesting relationships between striatal dopaminergic function and NMS. The basal ganglia are implicated in the modulation and integration of sensory information and pain, bladder function is under control of both inhibitory (D1) and facilitatory (D2) dopaminergic inputs, finally reduced dopaminergic activity in the mesocortical and mesolimbic pathways is involved in the development of several NMS including mood, motivational, and cognitive alterations...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28802560/traumatic-brain-injuries-during-development-disrupt-dopaminergic-signaling
#7
Kate Karelina, Kristopher R Gaier, Zachary M Weil
Traumatic brain injuries (TBI) sustained during peri-adolescent development produce lasting neuro-behavioral changes that render individuals at an increased risk for developing substance abuse disorders. Experimental and clinical evidence of a prolonged period of hypodopaminergia after TBI have been well documented, but the effect of juvenile TBI on dopaminergic dysfunction and its relationship with substance abuse have not been investigated. In order to determine the effect of juvenile brain injury on dopaminergic signaling, female mice were injured at 21days of age and then beginning seven weeks later were assessed for behavioral sensitization to amphetamine, a drug that increases synaptic dopamine availability...
August 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28800937/vortioxetine-a-new-alternative-for-the-treatment-of-major-depressive-disorder
#8
Estela Salagre, Iria Grande, Brisa Solé, Jose Sanchez-Moreno, Eduard Vieta
Major Depressive Disorder (MDD) is a serious psychiatric condition. Its treatment remains a challenge nowadays. Vortioxetine is a novel antidepressant with a unique profile, as it acts as a multimodal serotoninergic agent. Its efficacy in MDD has been established in many short- and long-term studies, with 7 positive, 4 negative and 1 failed randomized controlled trials. Moreover, its ability to modulate a wide range of neurotransmitters (serotonin, dopamine, norepinephrine, histamine, glutamate or GABA) confers vortioxetine pro-cognitive effects...
August 8, 2017: Revista de Psiquiatrí́a y Salud Mental
https://www.readbyqxmd.com/read/28800113/biomarker-research-in-parkinson-s-disease-using-metabolite-profiling
#9
REVIEW
Jesper F Havelund, Niels H H Heegaard, Nils J K Færgeman, Jan Bert Gramsbergen
Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifactorial disease, which requires a more precise diagnosis and personalized medication to obtain optimal outcome. In recent years, advanced metabolite profiling of body fluids like serum/plasma, CSF or urine, known as "metabolomics", has become a powerful and promising tool to identify novel biomarkers or "metabolic fingerprints" characteristic for PD at various stages of disease...
August 11, 2017: Metabolites
https://www.readbyqxmd.com/read/28790900/maladaptive-decision-making-in-adults-with-a-history-of-adolescent-alcohol-use-in-a-preclinical-model-is-attributable-to-the-compromised-assignment-of-incentive-value-during-stimulus-reward-learning
#10
Lauren C Kruse, Abigail G Schindler, Rapheal G Williams, Sophia J Weber, Jeremy J Clark
According to recent WHO reports, alcohol remains the number one substance used and abused by adolescents, despite public health efforts to curb its use. Adolescence is a critical period of biological maturation where brain development, particularly the mesocorticolimbic dopamine system, undergoes substantial remodeling. These circuits are implicated in complex decision making, incentive learning and reinforcement during substance use and abuse. An appealing theoretical approach has been to suggest that alcohol alters the normal development of these processes to promote deficits in reinforcement learning and decision making, which together make individuals vulnerable to developing substance use disorders in adulthood...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28783931/low-retinal-dehydrogenase-1-raldh1-level-in-prepubertal-boys-with-autism-spectrum-disorder-a-possible-link-to-dopamine-dysfunction
#11
Denis Pavăl, Florina Rad, Răzvan Rusu, Alexandru-Ştefan Niculae, Horaţiu Alexandru Colosi, Iuliana Dobrescu, Eleonora Dronca
Objective: Retinal dehydrogenase 1 (RALDH1) is a cytosolic enzyme which acts both as a source of retinoic acid (RA) and as a detoxification enzyme. RALDH1 has key functions in the midbrain dopaminergic system, which influences motivation, cognition, and social behavior. Since dopamine has been increasingly linked to autism spectrum disorder (ASD), we asked whether RALDH1 could contribute to the autistic phenotype. Therefore, we investigated for the first time the levels of RALDH1 in autistic patients...
August 31, 2017: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28781202/biomarkers-for-cognitive-dysfunction-in-parkinson-s-disease
#12
Lorraine V Kalia
INTRODUCTION: Cognitive dysfunction is among the most prevalent and debilitating non-motor features of Parkinson's disease (PD). The neuropathological correlates of cognitive dysfunction in PD are being revealed by clinicopathological correlation studies. These findings are fostering the development of candidate biomarkers to facilitate diagnosis of cognitive impairment and dementia, and to predict cognitive decline and onset of dementia in PD. METHODS: A literature review of candidate biomarkers for cognitive dysfunction in PD was performed based on a PubMed search for peer-reviewed articles published from 1997 to June 2017 using the search terms "biomarker", "parkinson", and "dementia"...
July 24, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28781201/seven-tesla-mri-of-the-substantia-nigra-in-patients-with-rapid-eye-movement-sleep-behavior-disorder
#13
Daniela Frosini, Mirco Cosottini, Graziella Donatelli, Mauro Costagli, Laura Biagi, Claudio Pacchetti, Michele Terzaghi, Pietro Cortelli, Dario Arnaldi, Enrica Bonanni, Michela Tosetti, Ubaldo Bonuccelli, Roberto Ceravolo
INTRODUCTION: Susceptibility-weighted imaging of the substantia nigra (SN) both at 7 and 3 Tesla (T) has shown high accuracy in distinguishing patients with Parkinson's disease (PD) and healthy subjects (HS). Patients with rapid eye movement (REM) behavior disorder (RBD) can develop synucleinopathies, and such risk is higher with dopamine transporter single photon emission tomography (123I-FP-CIT SPECT) evidence of nigro-striatal dysfunction. We aimed at evaluating SN 7T magnetic resonance imaging (7T-MRI) in patients with RBD and determining the agreement between MRI and 123I-FP-CIT SPECT...
August 2, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28780783/implications-of-circadian-rhythm-in-dopamine-and-mood-regulation
#14
REVIEW
Jeongah Kim, Sangwon Jang, Han Kyoung Choe, Sooyoung Chung, Gi Hoon Son, Kyungjin Kim
Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm...
July 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28777173/restless-legs-syndrome-and-sleep-related-movement-disorders
#15
Lynn Marie Trotti
PURPOSE OF REVIEW: This article provides an update on six sleep-related movement disorders: restless legs syndrome (RLS), periodic limb movement disorder, sleep-related leg cramps, bruxism, rhythmic movement disorder, and propriospinal myoclonus, with an emphasis on RLS. RECENT FINDINGS: RLS is a common sensorimotor disorder that impairs quality of life. RLS is frequently comorbid to neurologic, psychiatric, vascular, and inflammatory diseases. Accumulating evidence implicates the pathophysiology of RLS as a state of dopamine dysfunction and iron deficiency that occurs on a background of genetic susceptibility conferred by 6 gene polymorphisms...
August 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/28771182/new-targets-for-schizophrenia-treatment-beyond-the-dopamine-hypothesis
#16
REVIEW
Albert C Yang, Shih-Jen Tsai
Schizophrenia has been primarily associated with dopamine dysfunction, and treatments have been developed that target the dopamine pathway in the central nervous system. However, accumulating evidence has shown that the core pathophysiology of schizophrenia might involve dysfunction in dopaminergic, glutamatergic, serotonergic, and gamma-aminobutyric acid (GABA) signaling, which may lead to aberrant functioning of interneurons that manifest as cognitive, behavioral, and social dysfunction through altered functioning of a broad range of macro- and microcircuits...
August 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28763613/the-importance-of-mitophagy-in-maintaining-mitochondrial-function-in-u373mg-cells-bafilomycin-a1-restores-aminochrome-induced-mitochondrial-damage
#17
Sandro Huenchuguala, Patricia Muñoz, Juan Segura-Aguilar
Aminochrome, an orthoquinone formed during the dopamine oxidation of neuromelanin, is neurotoxic because it induces mitochondria dysfunction, protein degradation dysfunction (both autophagy and proteasomal systems), α-synuclein aggregation to neurotoxic oligomers, neuroinflammation, and oxidative and endoplasmic reticulum stress. In this study, we investigated the relationship between aminochrome-induced autophagy/lysosome dysfunction and mitochondrial dysfunction in U373MGsiGST6 cells. Aminochrome (75 μM) induces mitochondrial dysfunction as determined by (i) a significant decrease in ATP levels (70%; P < 0...
August 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28761417/on-the-role-of-endogenous-neurotoxins-and-neuroprotection-in-parkinson-s-disease
#18
REVIEW
Juan Segura-Aguilar
For 50 years ago was introduced L-3,4-dihydroxyphenylalanine (L-dopa) in Parkinson's disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson's disease...
June 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28758318/the-role-of-neurotransmitters-in-the-development-of-parkinson-s-disease-related-psychosis
#19
REVIEW
S A Factor, W M McDonald, F C Goldstein
Psychotic symptoms are common, disabling non-motor features of Parkinson's disease (PD). Despite noted heterogeneity in clinical features, natural history and therapy response, current dogma posits that psychosis generally progresses in a stereotypic manner through a cascade of events that begins with minor hallucinations and evolves to severe hallucinations and delusions. Further, the occurrence of psychotic symptoms is believed to indicate a poor prognosis. Here we propose a classification scheme that outlines the pathogenesis of psychosis as it relates to dysfunction of several neurotransmitter systems...
July 31, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28750400/a-dopamine-hypothesis-of-autism-spectrum-disorder
#20
Denis Pavăl
Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system...
July 28, 2017: Developmental Neuroscience
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