GeNeDis 2018: Genetics and Neurodegeneration [1st ed.] 9783030326326, 9783030326333

Table of contents :
Front Matter ....Pages i-xii
In Silico and In Vivo Studies on Quercetin as Potential Anti-Parkinson Agent (Hemanth Kumar Boyina, Sree Lakshmi Geethakhrishnan, Swetha Panuganti, Kiran Gangarapu, Krishna Prasad Devarakonda, Vasudha Bakshi et al.)....Pages 1-11
Exhaled Breath Condensate (EBC): Is It a Viable Source of Biomarkers for Lung Diseases? (Stefanos Patsiris, Themis Exarchos, Panayiotis Vlamos)....Pages 13-18
Treatment Development for Alzheimer’s Disease: How Are We Doing? (Constantin George Lyketsos)....Pages 19-19
Microbiome Hijacking Towards an Integrative Pest Management Pipeline (Vasiliki Lila Koumandou, Louis Papageorgiou, Spyridon Champeris Tsaniras, Aegli Papathanassopoulou, Marianna Hagidimitriou, Nikos Cosmidis et al.)....Pages 21-32
Regulation and Roles of Autophagy in the Brain (Nektarios Tavernarakis)....Pages 33-33
Three-Dimensional Models for Studying Neurodegenerative and Neurodevelopmental Diseases (Stavroula Tsaridou, Margarita Skamnelou, Marianna Iliadou, Georgia Lokka, Evangelia Parlapani, Maria Mougkogianni et al.)....Pages 35-41
Assessment of Factors Contributing to the Enhancement of Memory and Cognitive Abilities in the Context of Neurosciences (Spyridon Ktenas)....Pages 43-47
Buccal Mucosa Biomarkers in Alzheimer’s Disease (Antigoni Avramouli, Panayiotis Vlamos)....Pages 49-56
Engaging Social Interest and Creating Awareness for the Behavioural and Psychological Symptoms of Dementia (Kristine Newman)....Pages 57-57
Structural Study of the DNA: Clock/Bmal1 Complex Provides Insights for the Role of Cortisol, hGR, and HPA Axis in Stress Management and Sleep Disorders (Sofia Raftopoulou, Nicolas C. Nicolaides, Louis Papageorgiou, Anastasia Amfilochiou, Spyros G. Zakinthinos, Potamitis George et al.)....Pages 59-71
The Effects of Quantum Entanglement on Chromatin and Gene Expression (Michael Harney)....Pages 73-76
Olive Oil Polyphenols in Neurodegenerative Pathologies (Constantinos Salis, Louis Papageorgiou, Eleni Papakonstantinou, Marianna Hagidimitriou, Dimitrios Vlachakis)....Pages 77-91
Human Pluripotent Stem Cells as In Vitro Models of Neurodegenerative Diseases (Vasiliki Machairaki)....Pages 93-94
Nutritional Lipidomics in Alzheimer’s Disease (Efstathia Kalli)....Pages 95-104
Alzheimer’s Disease Therapeutic Approaches (Maria Revi)....Pages 105-116
Stress and Wellbeing of Psychiatry Trainees: A Literature Review (Rhoda Lai, Christos Plakiotis)....Pages 117-126
Brief Cognitive Tests in the Case of Dementia and Alzheimer’s Disease Early Diagnosis (Maria Sagiadinou, Antonia Plerou)....Pages 127-135
Synthesis, Molecular Docking Studies and Biological Evaluation of N-Acylarylhydrazones as Anti-Inflammatory Agents (Tangirala Sarala Devi, Galla Rajitha, Konda Swathi, Katari Sudheer Kumar, Amineni Umamaheswari)....Pages 137-148
Exosome Biomarkers Revolutionize Preclinical Diagnosis of Neurodegenerative Diseases and Assessment of Treatment Responses in Clinical Trials (Dimitrios Kapogiannis)....Pages 149-149
Biomarkers as a Different Approach in Prevention and Treatment of Drug Addiction (Preliminary Study) (Maria Gonidi, Anna Tselenti, Antonia Plerou)....Pages 151-154
Sleep Disorders and Restless Legs Syndrome in Hemodialysis Patients in Greece: A Cross-Sectional Study (Pantelis Stergiannis, Maria Govari, Edison Jahaj, Christina Marvaki, Georgia Toulia, Katerina Marvaki et al.)....Pages 155-162
Craniofacial and Neurological Phenotype in a Patient with De Novo 18q Microdeletion and 18p Microduplication (Christos Yapijakis, Antonia Angelopoulou, Emmanuel Manolakos, Costas Voumvourakis)....Pages 163-166
What Do Recent Clinical Trials Teach Us About the Etiology of AD (Nikolaos K. Robakis)....Pages 167-167
Developmental Biology and Transgenic Avian Embryology: Body Alterity Bioart Wet Lab (Adam Zaretsky)....Pages 169-176
Gene Editing, Sexual Reproduction, and the Arts: The Present, the Future, and the Imagined (Roberta Buiani)....Pages 177-177
Amyotrophic Lateral Sclerosis: Current Status in Diagnostic Biomarkers (Katerina Kadena, Panayiotis Vlamos)....Pages 179-187
Synthesis and Characterization of Biologically Significant 5-[N,N-dialkylamino alkoxy] azaindole 2-one, 3-thiosemicarbazones and 5-[N,N-dialkylamino alkoxy] azaindole 3-hydrazone, 2-ones (Konda Swathi, Galla Rajitha, Manda Sarangapani)....Pages 189-198
Genetic Counseling for Adult-Onset Spinal and Bulbar Muscular Atrophy (Kennedy Syndrome): Multiple Cases of Prenatal Testing in a Family (Christos Yapijakis, Achilleas Laskaratos, Antonia Angelopoulou, Costas Voumvourakis)....Pages 199-204
Transcriptomics and Metabolomics in Amyotrophic Lateral Sclerosis (Marios G. Krokidis)....Pages 205-212
Ocimum Sanctum Linn: A Potential Adjunct Therapy for Hyperhomocysteinemia-Induced Vascular Dementia (Jagadeesh Prasad Pasangulapati, Arun Reddy Ravula, Dinesh Reddy Kanala, Dinesh Kumar Bharatraj, Shanmukhi Boyina, Kiran Gangarapu et al.)....Pages 213-225
Alzheimer’s Disease: The Role of Mutations in Protein Folding (Eleftheria Polychronidou, Antigoni Avramouli, Panayiotis Vlamos)....Pages 227-236
Regulatory Role of MicroRNAs in Brain Development and Function (Christos Yapijakis)....Pages 237-247
The Misfolding of Proteins (Agathi Argyrou)....Pages 249-254
Back Matter ....Pages 255-262

Citation preview

Advances in Experimental Medicine and Biology 1195

Panayiotis Vlamos   Editor

GeNeDis 2018

Genetics and Neurodegeneration

Advances in Experimental Medicine and Biology Volume 1195

Series Editors Wim E. Crusio, CNRS and University of Bordeaux UMR 5287, Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, Pessac Cedex, France John D. Lambris, University of Pennsylvania, Philadelphia, PA, USA Heinfried H. Radeke, Clinic of the Goethe University Frankfurt Main, Institute of Pharmacology & Toxicology, Frankfurt am Main, Germany Nima Rezaei, Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

More information about this series at http://www.springer.com/series/5584

Panayiotis Vlamos Editor

GeNeDis 2018 Genetics and Neurodegeneration

Editor Panayiotis Vlamos Department of Informatics Ionian University Corfu, Greece

ISSN 0065-2598     ISSN 2214-8019 (electronic) Advances in Experimental Medicine and Biology ISBN 978-3-030-32632-6    ISBN 978-3-030-32633-3 (eBook) https://doi.org/10.1007/978-3-030-32633-3 © Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

To my father… who is gone.

Acknowledgment

I would like to thank Konstantina Skolariki for the help she provided during the editorial process.

vii

Contents

I n Silico and In Vivo Studies on Quercetin as Potential Anti-Parkinson Agent��������������������������������������������������������������������������������������    1 Hemanth Kumar Boyina, Sree Lakshmi Geethakhrishnan, Swetha Panuganti, Kiran Gangarapu, Krishna Prasad Devarakonda, Vasudha Bakshi, and Sandhya Rani Guggilla  xhaled Breath Condensate (EBC): Is It a Viable Source E of Biomarkers for Lung Diseases?������������������������������������������������������������������   13 Stefanos Patsiris, Themis Exarchos, and Panayiotis Vlamos  reatment Development for Alzheimer’s Disease: T How Are We Doing?����������������������������������������������������������������������������������������   19 Constantin George Lyketsos  icrobiome Hijacking Towards an Integrative Pest M Management Pipeline��������������������������������������������������������������������������������������   21 Vasiliki Lila Koumandou, Louis Papageorgiou, Spyridon Champeris Tsaniras, Aegli Papathanassopoulou, Marianna Hagidimitriou, Nikos Cosmidis, and Dimitrios Vlachakis  egulation and Roles of Autophagy in the Brain������������������������������������������   33 R Nektarios Tavernarakis  hree-Dimensional Models for Studying Neurodegenerative T and Neurodevelopmental Diseases ����������������������������������������������������������������   35 Stavroula Tsaridou, Margarita Skamnelou, Marianna Iliadou, Georgia Lokka, Evangelia Parlapani, Maria Mougkogianni, Rodolfos-­Iosif Danalatos, Anastasia Kanellou, Dimitris-David Chlorogiannis, Christina Kyrousi, and Stavros Taraviras

ix

x

Contents

 ssessment of Factors Contributing to the Enhancement of Memory A and Cognitive Abilities in the Context of Neurosciences������������������������������   43 Spyridon Ktenas Buccal Mucosa Biomarkers in Alzheimer’s Disease ������������������������������������   49 Antigoni Avramouli and Panayiotis Vlamos  ngaging Social Interest and Creating Awareness for the Behavioural E and Psychological Symptoms of Dementia����������������������������������������������������   57 Kristine Newman  tructural Study of the DNA: Clock/Bmal1 Complex Provides S Insights for the Role of Cortisol, hGR, and HPA Axis in Stress Management and Sleep Disorders������������������������������������������������������������������   59 Sofia Raftopoulou, Nicolas C. Nicolaides, Louis Papageorgiou, Anastasia Amfilochiou, Spyros G. Zakinthinos, Potamitis George, Elias Eliopoulos, George P. Chrousos, and Dimitrios Vlachakis  he Effects of Quantum Entanglement on Chromatin T and Gene Expression ��������������������������������������������������������������������������������������   73 Michael Harney  live Oil Polyphenols in Neurodegenerative Pathologies����������������������������   77 O Constantinos Salis, Louis Papageorgiou, Eleni Papakonstantinou, Marianna Hagidimitriou, and Dimitrios Vlachakis  uman Pluripotent Stem Cells as In Vitro Models H of Neurodegenerative Diseases������������������������������������������������������������������������   93 Vasiliki Machairaki Nutritional Lipidomics in Alzheimer’s Disease ��������������������������������������������   95 Efstathia Kalli Alzheimer’s Disease Therapeutic Approaches����������������������������������������������  105 Maria Revi  tress and Wellbeing of Psychiatry Trainees: A Literature Review������������  117 S Rhoda Lai and Christos Plakiotis  rief Cognitive Tests in the Case of Dementia and Alzheimer’s B Disease Early Diagnosis����������������������������������������������������������������������������������  127 Maria Sagiadinou and Antonia Plerou  ynthesis, Molecular Docking Studies and Biological Evaluation S of N-Acylarylhydrazones as Anti-­Inflammatory Agents������������������������������  137 Tangirala Sarala Devi, Galla Rajitha, Konda Swathi, Katari Sudheer Kumar, and Amineni Umamaheswari

Contents

xi

 xosome Biomarkers Revolutionize Preclinical Diagnosis E of Neurodegenerative Diseases and Assessment of Treatment Responses in Clinical Trials����������������������������������������������������������������������������  149 Dimitrios Kapogiannis  iomarkers as a Different Approach in Prevention and Treatment B of Drug Addiction (Preliminary Study) ��������������������������������������������������������  151 Maria Gonidi, Anna Tselenti, and Antonia Plerou  leep Disorders and Restless Legs Syndrome in Hemodialysis S Patients in Greece: A Cross-Sectional Study ������������������������������������������������  155 Pantelis Stergiannis, Maria Govari, Edison Jahaj, Christina Marvaki, Georgia Toulia, Katerina Marvaki, Georgia Chasioti, and George Intas  raniofacial and Neurological Phenotype in a Patient C with De Novo 18q Microdeletion and 18p Microduplication ����������������������  163 Christos Yapijakis, Antonia Angelopoulou, Emmanuel Manolakos, and Costas Voumvourakis  hat Do Recent Clinical Trials Teach Us About the Etiology of AD����������  167 W Nikolaos K. Robakis  evelopmental Biology and Transgenic Avian Embryology: D Body Alterity Bioart Wet Lab ������������������������������������������������������������������������  169 Adam Zaretsky  ene Editing, Sexual Reproduction, and the Arts: The Present, G the Future, and the Imagined�������������������������������������������������������������������������  177 Roberta Buiani  myotrophic Lateral Sclerosis: Current Status in Diagnostic A Biomarkers ������������������������������������������������������������������������������������������������������  179 Katerina Kadena and Panayiotis Vlamos  ynthesis and Characterization of Biologically Significant S 5-[N,N-­­dialkylamino alkoxy] azaindole 2-one, 3-thiosemicarbazones and 5-[N,N-­dialkylamino alkoxy] azaindole 3-hydrazone, 2-ones��������������  189 Konda Swathi, Galla Rajitha, and Manda Sarangapani  enetic Counseling for Adult-Onset Spinal and Bulbar G Muscular Atrophy (Kennedy Syndrome): Multiple Cases of Prenatal Testing in a Family ����������������������������������������������������������������������  199 Christos Yapijakis, Achilleas Laskaratos, Antonia Angelopoulou, and Costas Voumvourakis  ranscriptomics and Metabolomics in Amyotrophic Lateral Sclerosis������  205 T Marios G. Krokidis

xii

Contents

 cimum Sanctum Linn: A Potential Adjunct Therapy O for Hyperhomocysteinemia-Induced Vascular Dementia����������������������������  213 Jagadeesh Prasad Pasangulapati, Arun Reddy Ravula, Dinesh Reddy Kanala, Dinesh Kumar Bharatraj, Shanmukhi Boyina, Kiran Gangarapu, and Hemanth Kumar Boyina Alzheimer’s Disease: The Role of Mutations in Protein Folding����������������  227 Eleftheria Polychronidou, Antigoni Avramouli, and Panayiotis Vlamos  egulatory Role of MicroRNAs in Brain Development and Function��������  237 R Christos Yapijakis  he Misfolding of Proteins������������������������������������������������������������������������������  249 T Agathi Argyrou Index������������������������������������������������������������������������������������������������������������������  255

In Silico and In Vivo Studies on Quercetin as Potential Anti-Parkinson Agent Hemanth Kumar Boyina, Sree Lakshmi Geethakhrishnan, Swetha Panuganti, Kiran Gangarapu, Krishna Prasad Devarakonda, Vasudha Bakshi, and Sandhya Rani Guggilla

1  Introduction Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder and is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of proteinaceous cytoplasmic inclusions known as Lewy bodies (LBs) (Michel et al. 2016; Chauhan and Jeans 2015). Central nervous system dysfunction in PD patients results in symptoms such as bradykinesia, resting tremors, postural instability, and muscular rigidity (Jankovic 2008). Recent studies have provided insight into the major events involved in PD pathogenesis, including mitochondrial dysfunction and proteasome system dysfunction (Ghiglieri et al. 2018). Alpha-synuclein is the major protein constituent of LBs and Lewy neuritis aggregation. It is also linked with the accumulation of misfolded or damaged proteins and oxidative stress in the substantia nigra (Yan et al. 2018). Rotenone, a neurotoxin that belongs to the family of isoflavones, naturally found in the roots and stems of several plants, is used as a broad-spectrum pesticide. It is highly lipophilic, thus easily crossing the BBB. Once in the cell, rotenone accumulates at mitochondrial complex I where it inhibits the transfer of electrons from iron-sulfur (Fe-S) centers to ubiquinone (Gowthami et al. 2018). Increased reactive oxygen species production has been associated with complex I dysfunction induced by rotenone, which may produce oxidative damage to DNA

H. K. Boyina (*) · S. L. Geethakhrishnan · S. Panuganti · K. Gangarapu K. P. Devarakonda · V. Bakshi School of Pharmacy, Anurag Group of Institutions, Hyderabad, Telangana, India S. R. Guggilla University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, India © Springer Nature Switzerland AG 2020 P. Vlamos (ed.), GeNeDis 2018, Advances in Experimental Medicine and Biology 1195, https://doi.org/10.1007/978-3-030-32633-3_1

1

2

H. K. Boyina et al.

and proteins of neural cells, hence leading to the death of DA neuron (Surmeier 2018; Gould et al. 2018). Currently, levodopa (L-dopa), although is considered a gold standard replacement therapy in PD, so far only alleviates the clinical symptoms. Furthermore, patients usually experience severe side effects several years after the L-dopa treatment. Therefore, efforts are made not only to improve the effect of L-dopa treatment for PD but also to investigate new drugs with both anti-­ parkinsonian and neuroprotective effects (Cenci and Crossman 2018). Growing evidence suggests that abnormal redox active metal accumulation caused by dysregulation plays a central role in the neuropathology of PD. Redox active metals like Fe and Cu catalyze essential reactions for brain functions. However, these metals can also participate in the generation of highly toxic free radicals (fenton reaction) that can cause oxidative damage to cells and ultimately lead to the death of dopaminergic neurons (Aguilera et al. 2018). Flavonoids are naturally occurring plant molecules that are able to bind to free iron atoms and also offer powerful antioxidant protection. Quercetin, a polyphenolic compound, chelates iron atoms involved in fenton reaction in L-dopa metabolism hence acts as powerful iron-chelating agent. Quercetin’s antioxidant effects are closely related to iron-chelating capacity which accounts for its ability to prevent neurodegeneration in Parkinson’s disease (Castañeda-Arriaga et al. 2018). Recent studies suggest the neuropharmacological efficacy of polyphenolic quercetin against Parkinson’s disease (Sarubbo et al. 2018). This study is designed to investigate the ameliorative role of quercetin with and without L-dopa in rotenone-induced Parkinson’s disease (El-Horany et al. 2016; Kabel et al. 2018).

2  Materials and Methods Forty-two adult male Wistar rats aged 7 weeks, weighing 150–250 g, were used. All animals were maintained under standard husbandry conditions. The rats were randomly assigned to six groups (n = 6) (Table. 1), and the experimental protocol was duly approved by the Institutional Animal Ethics Committee, and study design is Table 1  Animal grouping Groups I II III IV V VI VII

Treatment Served as normal control group received vehicle (control) Parkinsonism was induced by subcutaneous administration of rotenone for 28 days at a dose of 1.5 mg/kg (rotenone-R) Co-treated with rotenone and L-dopa (R-L-dopa) Co-treated with rotenone and low dose of quercetin. (R + LD of quercetin) Co-treated with rotenone and high dose of quercetin (R + HD of quercetin) Co-treated with rotenone and low dose of quercetin and L-dopa (R + LD of quercetin + L-dopa) Co-treated with rotenone and high dose of quercetin and L-dopa (R + HD of quercetin + L-dopa)

In Silico and In Vivo Studies on Quercetin as Potential Anti-Parkinson Agent

3

Fig. 1  Study design (duration of drug treatment and parameters assessment)

depicted in Fig. 1. Rotenone was dissolved in 1% DMSO solution and administered subcutaneously daily for 28 days at a dose of 1.5 mg/kg. Quercetin and L-dopa were dissolved in sterile water for injection, and quercetin was given at 15 mg/kg and 50  mg/kg doses. L-dopa and carbidopa were given in 1:10 ratio at doses of 20  mg/kg and 2  mg/kg  i.p. All treatments were given 1  h prior to the rotenone administration from 15th to 28th day. The body weight of animals was measured prior to rotenone administration (first day) and on the last day of the study (28th day). The percentage change in body weight was calculated as follows: change in bodyweight = [(first day body weight−28th day body weight)/first day body weight] x100. Behavioral parameters like catalepsy, grip strength, and locomotor activity on rotarod were assessed on 14th, 21st, and 28th day of the study. Terminally on 29th day, the rats were sacrificed, and the striatum was separated. The 10% homogenate of striatum was made in 0.9% cold saline and used for biochemical assays (superoxide dismutase (SOD), catalase, reduced glutathione (GSH), and hydrogen peroxide (H2O2)). In addition to the iron-chelating activity of quercetin, serum iron assay was also determined. All antioxidant assays were carried out according to earlier described procedures (Hemanth Kumar et al. 2016; Hemanth Kumar et al. 2017; Boyina et al. 2018). Catalepsy test was carried out according to the method described by Costall 1974 (Costall and Naylor 1974). Rotarod was evaluated by the method as described by Kelly et al. (1998). Molecular docking studies were carried out using MOE in order to predict the possible binding interactions of quercetin with aromatic L-amino acid decarboxylase (AADC) and catechol-O-methyltransferase (hCOMT)(Ruddarraju et al. 2019). The crystal structure of the protein was retrieved from a protein data bank (http://www.rcsb.com). Statistical Analysis: The data was statistically analyzed, using Graph Pad prism 5.0, and all values are mentioned as mean  ±  SEM.  The behavioral data were analyzed using two-way analysis of variance (ANOVA) followed by Bonferroni post hoc test for multiple comparisons. For biochemical parameters, one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test and then by Dunnett’s multiple range tests was performed. The statistical significance of difference was taken as P