Methods for Creating Fly Models to Understand the Molecular Mechanisms Underlying Neurological Diseases

2019 ◽  
pp. 37-54
Author(s):  
Nandan J. ◽  
Sonal Nagarkar-Jaiswal
Keyword(s):  
Molecular Mechanisms ◽  
Neurological Diseases

scholarly journals Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou
Keyword(s):  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Cellular Processes ◽  
Dna And Rna ◽  
Chemotherapeutic Response ◽  
Non Coding Rna ◽  
Response To Chemotherapy ◽  
Personalized Oncology ◽  
Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

scholarly journals Molecular mechanisms of metabotropic GABAB receptor function

2021 ◽  
Vol 7 (22) ◽  
pp. eabg3362
Author(s):  
Hamidreza Shaye ◽  
Benjamin Stauch ◽  
Cornelius Gati ◽  
Vadim Cherezov
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Gabab Receptor ◽  
Neurological Diseases ◽  
Activation Mechanism ◽  
Allosteric Modulators ◽  
Inhibitory Neurotransmitter ◽  
Therapeutic Drugs ◽  
G Protein Coupled ◽  
The Brain

Metabotropic γ-aminobutyric acid G protein–coupled receptors (GABAB) represent one of the two main types of inhibitory neurotransmitter receptors in the brain. These receptors act both pre- and postsynaptically by modulating the transmission of neuronal signals and are involved in a range of neurological diseases, from alcohol addiction to epilepsy. A series of recent cryo-EM studies revealed critical details of the activation mechanism of GABAB. Structures are now available for the receptor bound to ligands with different modes of action, including antagonists, agonists, and positive allosteric modulators, and captured in different conformational states from the inactive apo to the fully active state bound to a G protein. These discoveries provide comprehensive insights into the activation of the GABAB receptor, which not only broaden our understanding of its structure, pharmacology, and physiological effects but also will ultimately facilitate the discovery of new therapeutic drugs and neuromodulators.

scholarly journals Molecular mechanisms of cell death in neurological diseases

2021 ◽  
Author(s):  
Diane Moujalled ◽  
Andreas Strasser ◽  
Jeffrey R. Liddell
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Response To Therapy ◽  
Signalling Cascades ◽  
The Brain

AbstractTightly orchestrated programmed cell death (PCD) signalling events occur during normal neuronal development in a spatially and temporally restricted manner to establish the neural architecture and shaping the CNS. Abnormalities in PCD signalling cascades, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and cell death associated with autophagy as well as in unprogrammed necrosis can be observed in the pathogenesis of various neurological diseases. These cell deaths can be activated in response to various forms of cellular stress (exerted by intracellular or extracellular stimuli) and inflammatory processes. Aberrant activation of PCD pathways is a common feature in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, resulting in unwanted loss of neuronal cells and function. Conversely, inactivation of PCD is thought to contribute to the development of brain cancers and to impact their response to therapy. For many neurodegenerative diseases and brain cancers current treatment strategies have only modest effect, engendering the need for investigations into the origins of these diseases. With many diseases of the brain displaying aberrations in PCD pathways, it appears that agents that can either inhibit or induce PCD may be critical components of future therapeutic strategies. The development of such therapies will have to be guided by preclinical studies in animal models that faithfully mimic the human disease. In this review, we briefly describe PCD and unprogrammed cell death processes and the roles they play in contributing to neurodegenerative diseases or tumorigenesis in the brain. We also discuss the interplay between distinct cell death signalling cascades and disease pathogenesis and describe pharmacological agents targeting key players in the cell death signalling pathways that have progressed through to clinical trials.

scholarly journals Monoclonal Antibodies as Neurological Therapeutics

2021 ◽  
Vol 14 (2) ◽  
pp. 92
Author(s):  
Panagiotis Gklinos ◽  
Miranta Papadopoulou ◽  
Vid Stanulovic ◽  
Dimos D. Mitsikostas ◽  
Dimitrios Papadopoulos
Keyword(s):  
Monoclonal Antibodies ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Therapeutic Agents ◽  
Medical Specialties ◽  
Specific Effects ◽  
Different Types ◽  
Neurological Conditions ◽  
Disease Pathways

Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases. Untangling the molecular mechanisms of disease allows monoclonal antibodies to block disease pathways accurately and efficiently with exceptional target specificity, minimizing non-specific effects. On the other hand, accumulating experience shows that monoclonal antibodies may carry class-specific and target-associated risks. This article provides an overview of different types of monoclonal antibodies and their characteristics and reviews monoclonal antibodies currently in use or under development for neurological disease.

First person – Fanny Jaudon and Martina Albini

2021 ◽  
Vol 134 (16) ◽  
Keyword(s):  
Neurotrophic Factor ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Early Career ◽  
First Person ◽  
Early Career Researchers ◽  
And Function ◽  
The University ◽  
Selection Of

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Fanny Jaudon and Martina Albini are co-first authors on ‘ A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor’, published in JCS. Fanny is a postdoc at the University of Trieste in the lab of Lorenzo A. Cingolani at Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genova, Italy, investigating the molecular mechanisms controlling development and function of neuronal circuits and implementing genome-editing approaches for the treatment of neurological disorders. Martina is a PhD student at the Istituto Italiano di Tecnologia in the lab of Fabio Benfenati and Fabrizia Cesca investigating neurotrophin biology and its involvement in neurological diseases.

scholarly journals Stochastic left–right neuronal asymmetry in Caenorhabditis elegans

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150407 ◽  
Author(s):  
Amel Alqadah ◽  
Yi-Wen Hsieh ◽  
Rui Xiong ◽  
Chiou-Fen Chuang
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Calcium Signalling ◽  
Model Organism ◽  
Brain Asymmetry ◽  
C Elegans ◽  
Left And Right ◽  
Left Right Asymmetry ◽  
Neuronal Asymmetry

Left–right asymmetry in the nervous system is observed across species. Defects in left–right cerebral asymmetry are linked to several neurological diseases, but the molecular mechanisms underlying brain asymmetry in vertebrates are still not very well understood. The Caenorhabditis elegans left and right amphid wing ‘C’ (AWC) olfactory neurons communicate through intercellular calcium signalling in a transient embryonic gap junction neural network to specify two asymmetric subtypes, AWC OFF (default) and AWC ON (induced), in a stochastic manner. Here, we highlight the molecular mechanisms that establish and maintain stochastic AWC asymmetry. As the components of the AWC asymmetry pathway are highly conserved, insights from the model organism C. elegans may provide a window onto how brain asymmetry develops in humans. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

scholarly journals Role of Enzymes in Causing Neurological Disorders

2021 ◽  
Vol 12 (1) ◽  
pp. 466-476
Author(s):  
Vysakh Visweswaran ◽  
Roshni PR
Keyword(s):  
Neurological Disorders ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Direct Result ◽  
Permanent Disability ◽  
Genetic Abnormalities ◽  
Underlying Pathology

Diseases of the nervous system are always associated with poor prognosis and limited treatment options. The fragile nature of the neurons and their inability to replicate means that neurological disorders are associated with a permanent disability. Pharmacotherapy of neurological diseases requires understanding the molecular mechanisms involved in the disease pathology. In most of the cases a faulty cellular biochemical pathway is involved, resulting from a defective enzyme. This article focusses on role of enzymes in various neurological disorders. To review pertinent literature and summarise the role of enzymes in the underlying pathology of various neurological disorders. A comprehensive literature search was conducted using PubMed, SCOPUS, J-GATE and Google Scholar and relevant papers were collected using the keywords enzymes, Alzheimer's disease, redox, thiamine, depression, neurotransmitters, epileptogenesis. The literature review highlighted the role of enzymes in major neurological disorders and their potential to be used as drug targets and biomarkers. Identifying defective enzymes gives us new molecular targets to focus on for developing more effective pharmacotherapeutic options. They can be also considered as potential biomarkers. An abnormal enzyme is most often a direct result of an underlying genetic abnormality. Identifying and screening for these genetic abnormalities can be used in early identification and prevention of disease in individuals who have a genetic predisposition. The modern advances in genetic engineering shows a lot of promise in correcting these abnormalities and development of revolutionary cures although ethical concerns remain. 

Multimodal bioinformatic analyses of the neurodegenerative disease-associated TECPR2 gene reveal its diverse roles

2021 ◽  
pp. jmedgenet-2021-108193
Author(s):  
Ido Shalev ◽  
Judith Somekh ◽  
Alal Eran
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Expression Patterns ◽  
Population Variation ◽  
Functional Enrichment ◽  
Phylogenetic Profiling ◽  
Developing Neurons

BackgroundLoss of tectonin β-propeller repeat-containing 2 (TECPR2) function has been implicated in an array of neurodegenerative disorders, yet its physiological function remains largely unknown. Understanding TECPR2 function is essential for developing much needed precision therapeutics for TECPR2-related diseases.MethodsWe leveraged considerable amounts of functional data to obtain a comprehensive perspective of the role of TECPR2 in health and disease. We integrated expression patterns, population variation, phylogenetic profiling, protein-protein interactions and regulatory network data for a minimally biased multimodal functional analysis. Genes and proteins linked to TECPR2 via multiple lines of evidence were subject to functional enrichment analyses to identify molecular mechanisms involving TECPR2.ResultsTECPR2 was found to be part of a tight neurodevelopmental gene expression programme that includes KIF1A, ATXN1, TOM1L2 and FA2H, all implicated in neurological diseases. Functional enrichment analyses of TECPR2-related genes converged on a role in late autophagy and ribosomal processes. Large-scale population variation data demonstrated that this role is non-redundant.ConclusionsTECPR2 might serve as an indicator for the energy balance between protein synthesis and autophagy, and a marker for diseases associated with their imbalance, such as Alzheimer’s disease and Huntington’s disease. Specifically, we speculate that TECPR2 plays an important role as a proteostasis regulator during synaptogenesis, highlighting its importance in developing neurons. By advancing our understanding of TECPR2 function, this work provides an essential stepping stone towards the development of precision diagnostics and targeted treatment options for TECPR2-related disorders.

Integrative functional analyses of the neurodegenerative disease-associated TECPR2 gene reveal its diverse roles

2020 ◽  
Author(s):  
Ido Shalev ◽  
Judith Somekh ◽  
Alal Eran
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Expression Patterns ◽  
Population Variation ◽  
Functional Enrichment ◽  
Phylogenetic Profiling ◽  
Developing Neurons

Abstract BackgroundLoss of tectonin β-propeller repeat-containing 2 (TECPR2) function has been implicated in an array of neurodegenerative disorders, yet its physiological function remains largely unknown. Understanding TECPR2 function is essential for developing much needed precision therapeutics for TECPR2-related diseases. MethodsWe leveraged the considerable amounts of functional data to obtain a comprehensive perspective of the role of TECPR2 in health and disease. We integrated expression patterns, population variation, phylogenetic profiling, protein-protein interactions, and regulatory network data for a minimally biased multimodal functional analysis. Genes and proteins linked to TECPR2 via multiple lines of evidence were subject to functional enrichment analyses to identify molecular mechanisms involving TECPR2.ResultsTECPR2 was found to be part of a tight neurodevelopmental gene expression program that includes KIF1A, ATXN1, TOM1L2, and FA2H, all implicated in neurological diseases. Functional enrichment analyses of TECPR2-related genes converged on a role in late autophagy and ribosomal processes. Large-scale population variation data demonstrated that this role is nonredundant. ConclusionsTECPR2 might serve as an indicator for the energy balance between protein synthesis and autophagy, and a marker for diseases associated with their imbalance, such as Alzheimer’s disease, Huntington’s disease, and various cancers. Our work further suggests that TECPR2 plays a role as a synaptic proteostasis regulator during synaptogenesis, highlighting its importance in developing neurons. By advancing our understanding of TECPR2 function, this work provides an essential stepping stone towards the development of precision diagnostics and targeted treatment options for TECPR2-related disorders.

scholarly journals Protective Effects of Melatonin on Neurogenesis Impairment in Neurological Disorders and Its Relevant Molecular Mechanisms

2020 ◽  
Vol 21 (16) ◽  
pp. 5645
Author(s):  
Joseph Wai-Hin Leung ◽  
Kwok-Kuen Cheung ◽  
Shirley Pui-Ching Ngai ◽  
Hector Wing-Hong Tsang ◽  
Benson Wui-Man Lau
Keyword(s):  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Neurological Diseases ◽  
Protective Effects ◽  
Neurological Outcomes ◽  
Pathological Conditions ◽  
Neurological Illnesses ◽  
Neurological Conditions ◽  
Traditional Understanding

Neurogenesis is the process by which functional new neurons are generated from the neural stem cells (NSCs) or neural progenitor cells (NPCs). Increasing lines of evidence show that neurogenesis impairment is involved in different neurological illnesses, including mood disorders, neurogenerative diseases, and central nervous system (CNS) injuries. Since reversing neurogenesis impairment was found to improve neurological outcomes in the pathological conditions, it is speculated that modulating neurogenesis is a potential therapeutic strategy for neurological diseases. Among different modulators of neurogenesis, melatonin is a particularly interesting one. In traditional understanding, melatonin controls the circadian rhythm and sleep–wake cycle, although it is not directly involved in the proliferation and survival of neurons. In the last decade, it was reported that melatonin plays an important role in the regulation of neurogenesis, and thus it may be a potential treatment for neurogenesis-related disorders. The present review aims to summarize and discuss the recent findings regarding the protective effects of melatonin on the neurogenesis impairment in different neurological conditions. We also address the molecular mechanisms involved in the actions of melatonin in neurogenesis modulation.

Sign in / Sign up

Export Citation Format

Share Document