scholarly journals Neuroplastin in Neuropsychiatric Diseases

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1507
Author(s):  
Xiao Lin ◽  
Yi Liang ◽  
Rodrigo Herrera-Molina ◽  
Dirk Montag
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Neurological Diseases ◽  
Medical Intervention ◽  
Immunoglobulin Superfamily ◽  
Cell Recognition ◽  
Molecular Features ◽  
Neuropsychiatric Diseases ◽  
Neurological Processes

Molecular mechanisms underlying neuropsychiatric and neurodegenerative diseases are insufficiently elucidated. A detailed understanding of these mechanisms may help to further improve medical intervention. Recently, intellectual abilities, creativity, and amnesia have been associated with neuroplastin, a cell recognition glycoprotein of the immunoglobulin superfamily that participates in synapse formation and function and calcium signaling. Data from animal models suggest a role for neuroplastin in pathways affected in neuropsychiatric and neurodegenerative diseases. Neuroplastin loss or disruption of molecular pathways related to neuronal processes has been linked to various neurological diseases, including dementia, schizophrenia, and Alzheimer’s disease. Here, we review the molecular features of the cell recognition molecule neuroplastin, and its binding partners, which are related to neurological processes and involved in learning and memory. The emerging functions of neuroplastin may have implications for the treatment of diseases, particularly those of the nervous system.

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 Genetic control of age-related gene expression and complex traits in the human brain

2017 ◽  
Author(s):  
Trevor Martin ◽  
Hunter B. Fraser
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Genetic Variants ◽  
Complex Traits ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Expression Patterns ◽  
Related Gene ◽  
Age Related

AbstractAge is the primary risk factor for many of the most common human diseases—particularly neurodegenerative diseases—yet we currently have a very limited understanding of how each individual’s genome affects the aging process. Here we introduce a method to map genetic variants associated with age-related gene expression patterns, which we call temporal expression quantitative trait loci (teQTL). We found that these loci are markedly enriched in the human brain and are associated with neurodegenerative diseases such as Alzheimer’s disease and Creutzfeldt-Jakob disease. Examining potential molecular mechanisms, we found that age-related changes in DNA methylation can explain some cis-acting teQTLs, and that trans-acting teQTLs can be mediated by microRNAs. Our results suggest that genetic variants modifying age-related patterns of gene expression, acting through both cis- and trans-acting molecular mechanisms, could play a role in the pathogenesis of diverse neurological diseases.

scholarly journals Vascular endotelial dysfunction is a pathogenetic factor in the development of neurodegenerative diseases and cognitive impairment

2020 ◽  
pp. 11-26
Author(s):  
N. V. Goncharov ◽  
P. I. Popova ◽  
A. S. Golovkin ◽  
N. M. Zalutskaya ◽  
E. I. Palchikova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neurodegenerative Diseases ◽  
Positive Impact ◽  
Neurological Diseases ◽  
Organophosphate Poisoning ◽  
Clinical Consequence ◽  
Endothelial Monolayer ◽  
Cellular Mechanisms ◽  
Neuropsychiatric Diseases ◽  
Monogenic Diseases

The amount of publications devoted to the endothelial cells, on the one hand, and neurological diseases, on the other hand, has been growing rapidly in recent years. Nevertheless, the relationship between the endothelial monolayer and the cells of the nervous system remains poorly studied. This review presents the available information about endothelial markers, molecular and cellular mechanisms for maintaining the integrity of the endothelial monolayer and the violations in some acute and chronic neuropsychiatric diseases. At the molecular level, the most important pathogenetic link in endothelial dysfunction is an imbalance of Ca2+ ions, which is associated with redox imbalance in the cells and increased generation of reactive oxygen species. Genetic and epigenetic factors that cause these disorders and their cause-and-effect relationships are considered. Of the genetic diseases, the most studied are monogenic diseases associated with impaired blood-brain barrier integrity: this is a deficiency of protein molecules that ensure glucose transport, structural and functional integrity of tight junctions and the basement membrane of endothelial cells themselves, as well as mutations in pericytes and smooth muscle cells. Mutations that increase the risk of developing known neurodegenerative diseases, but are also the cause of cerebrovascular pathology, are less studied. The small vessel diseases constitute a whole group of primarily epigenetically caused diseases, the clinical consequence of which is often vascular dementia. Special attention is paid to one of the least studied problems—the pathogenesis of toxicological diseases that occur at different times after acute and chronic organophosphate poisoning. Microangiopathies caused by damage to the endothelium in the central and peripheral nervous systems can be the main cause for the development of delayed effects in organophosphate poisoning. In the absence of effective therapies for neurodegenerative diseases, more and more evidence is emerging about the positive impact of the nutritional structure and healthy lifestyle on the state of blood vessels and the risk of developing these diseases.

Excitotoxicity as a Target Against Neurodegenerative Processes

2020 ◽  
Vol 26 (12) ◽  
pp. 1251-1262 ◽  
Author(s):  
Octavio Binvignat ◽  
Jordi Olloquequi
Keyword(s):  
Neurodegenerative Diseases ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Mitochondrial Dysfunctions ◽  
Beneficial Effects ◽  
Clinical Investigations ◽  
Turn Over ◽  
Excitotoxic Cell Death ◽  
Lateral Sclerosis

: The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as the injury and death of neurons due to excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. : Despite the anti-excitotoxic drug memantine has shown modest beneficial effects in some patients with dementia, to date, there is no effective treatment capable of halting or curing neurodegenerative diseases such as Alzheimer’s disease, Parkinson disease, Huntington’s disease or amyotrophic lateral sclerosis. This has led to a growing body of research focusing on understanding the mechanisms associated with the excitotoxic insult and on uncovering potential therapeutic strategies targeting these mechanisms. : In the present review, we examine the molecular mechanisms related to excitotoxic cell death. Moreover, we provide a comprehensive and updated state of the art of preclinical and clinical investigations targeting excitotoxic- related mechanisms in order to provide an effective treatment against neurodegeneration.

Purines and Pyrimidines: Metabolism, Function and Potential as therapeutic options in neurodegenerative diseases

2020 ◽  
Vol 21 ◽  
Author(s):  
Debanjan Kundu ◽  
Vikash Kumar Dubey
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Treatment Regimens ◽  
Loss Of Balance ◽  
Current Scenario ◽  
Unexplored Area ◽  
Molecular Origin ◽  
Purines And Pyrimidines

Abstract:: Various neurodegenerative disorders have molecular origin but some common molecular mechanisms. In the current scenario, there are very few treatment regimens present for advanced neurodegenerative diseases. In this context, there is an urgent need for alternate options in the form of natural compounds with an ameliorating effect on patients. There have been individual scattered experiments trying to identify potential values of various intracellular metabolites. Purines and Pyrimidines, which are vital molecules governing various aspects of cellular biochemical reactions, have been long sought as crucial candidates for the same, but there are still many questions that go unanswered. Some critical functions of these molecules associated with neuromodulation activities have been identified. They are also known to play a role in foetal neurodevelopment, but there is a lacuna in understanding their mechanisms. In this review, we have tried to assemble and identify the importance of purines and pyrimidines, connecting them with the prevalence of neurodegenerative diseases. The leading cause of this class of diseases is protein misfolding and the formation of amyloids. A direct correlation between loss of balance in cellular homeostasis and amyloidosis is yet an unexplored area. This review aims at bringing the current literature available under one umbrella serving as a foundation for further extensive research in this field of drug development in neurodegenerative diseases.

The Protective Effects of Green Tea Catechins in the Management of Neurodegenerative Diseases: A Review

2019 ◽  
Vol 16 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Tahereh Farkhondeh ◽  
Hanieh Shaterzadeh Yazdi ◽  
Saeed Samarghandian
Keyword(s):  
Neurodegenerative Diseases ◽  
Signaling Pathways ◽  
Green Tea ◽  
Molecular Mechanisms ◽  
Main Role ◽  
Related Factor ◽  
Protective Effects ◽  
Tea Catechins ◽  
Green Tea Catechins ◽  
And Control

Background: The therapeutic strategies to manage neurodegenerative diseases remain limited and it is necessary to discover new agents for their prevention and control. Oxidative stress and inflammation play a main role in the pathogenesis of neurodegenerative diseases. The aim of this study is to review the effects of green tea catechins against the Neurodegenerative Diseases. Methods: In this study, we extensively reviewed all articles on the terms of Green tea, catechins, CNS disorders, and different diseases in PubMed, Science Direct, Scopus, and Google Scholar databases between the years 1990 and 2017. Results: The present study found that catechins, the major flavonoids in green tea, are powerful antioxidants and radical scavengers which possess the potential roles in the management of neurodegenerative diseases. Catechins modulate the cellular and molecular mechanisms through the inflammation-related NF-&amp;#954;B and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Conclusion: The findings of the present review shows catechins could be effective against neurodegenerative diseases due to their antioxidation and anti-inflammation effects and the involved biochemical pathways including Nrf2 and NF-kB signaling pathways.<P&gt;

scholarly journals Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms

2021 ◽  
Vol 10 (6) ◽  
pp. 1214
Author(s):  
Ji Tu ◽  
Jose Vargas Castillo ◽  
Abhirup Das ◽  
Ashish D. Diwan
Keyword(s):  
Cervical Myelopathy ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Disease Process ◽  
Classification Systems ◽  
Molecular Features ◽  
Formidable Challenge ◽  
Long Term Treatment ◽  
Degenerative Cervical Myelopathy

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.

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.

Biobanking for Neurodegenerative Diseases: Challenge for Translational Research and Data Privacy

2021 ◽  
pp. 107385842110366
Author(s):  
Emilia Giannella ◽  
Valentino Notarangelo ◽  
Caterina Motta ◽  
Giulia Sancesario
Keyword(s):  
Neurodegenerative Diseases ◽  
Translational Research ◽  
Data Protection ◽  
Biological Samples ◽  
Data Privacy ◽  
Neurological Diseases ◽  
Great Effort ◽  
General Data Protection Regulation ◽  
In Silico Studies

Biobanking has emerged as a strategic challenge to promote knowledge on neurological diseases, by the application of translational research. Due to the inaccessibility of the central nervous system, the advent of biobanks, as structure collecting biospecimens and associated data, are essential to turn experimental results into clinical practice. Findings from basic research, omics sciences, and in silico studies, definitely require validation in clinically well-defined cohorts of patients, even more valuable when longitudinal, or including preclinical and asymptomatic individuals. Finally, collecting biological samples requires a great effort to guarantee respect for transparency and protection of sensitive data of patients and donors. Since the European General Data Protection Regulation 2016/679 has been approved, concerns about the use of data in biomedical research have emerged. In this narrative review, we focus on the essential role of biobanking for translational research on neurodegenerative diseases. Moreover, we address considerations for biological samples and data collection, the importance of standardization in the preanalytical phase, data protection (ethical and legal) and the role of donors in improving research in this field.

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