scholarly journals The Calcium/Calmodulin-Dependent Kinases II and IV as Therapeutic Targets in Neurodegenerative and Neuropsychiatric Disorders

2021 ◽  
Vol 22 (9) ◽  
pp. 4307
Author(s):  
Kinga Sałaciak ◽  
Aleksandra Koszałka ◽  
Elżbieta Żmudzka ◽  
Karolina Pytka
Keyword(s):  
Drug Design ◽  
Therapeutic Targets ◽  
Neuropsychiatric Disorders ◽  
Cellular Functions ◽  
Calcium Calmodulin Dependent ◽  
Regulatory Processes ◽  
Neuropsychiatric Diseases ◽  
Future Drug ◽  
Structure And Functions

CaMKII and CaMKIV are calcium/calmodulin-dependent kinases playing a rudimentary role in many regulatory processes in the organism. These kinases attract increasing interest due to their involvement primarily in memory and plasticity and various cellular functions. Although CaMKII and CaMKIV are mostly recognized as the important cogs in a memory machine, little is known about their effect on mood and role in neuropsychiatric diseases etiology. Here, we aimed to review the structure and functions of CaMKII and CaMKIV, as well as how these kinases modulate the animals’ behavior to promote antidepressant-like, anxiolytic-like, and procognitive effects. The review will help in the understanding of the roles of the above kinases in the selected neurodegenerative and neuropsychiatric disorders, and this knowledge can be used in future drug design.

scholarly journals Vascular CaMKII: heart and brain in your arteries

2016 ◽  
Vol 311 (3) ◽  
pp. C462-C478 ◽  
Author(s):  
Fanny Toussaint ◽  
Chimène Charbel ◽  
Bruce G. Allen ◽  
Jonathan Ledoux
Keyword(s):  
Cellular Proliferation ◽  
Cell Function ◽  
Vascular System ◽  
Splice Variants ◽  
Cell Types ◽  
Cellular Functions ◽  
Vascular Cell ◽  
Calcium Calmodulin Dependent ◽  
Regulatory Processes ◽  
Neuronal Tissues

First characterized in neuronal tissues, the multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is a key signaling component in several mammalian biological systems. Its unique capacity to integrate various Ca2+ signals into different specific outcomes is a precious asset to excitable and nonexcitable cells. Numerous studies have reported roles and mechanisms involving CaMKII in brain and heart tissues. However, corresponding functions in vascular cell types (endothelium and vascular smooth muscle cells) remained largely unexplored until recently. Investigation of the intracellular Ca2+ dynamics, their impact on vascular cell function, the regulatory processes involved and more recently the spatially restricted oscillatory Ca2+ signals and microdomains triggered significant interest towards proteins like CaMKII. Heteromultimerization of CaMKII isoforms (four isoforms and several splice variants) expands this kinase's peculiar capacity to decipher Ca2+ signals and initiate specific signaling processes, and thus controlling cellular functions. The physiological functions that rely on CaMKII are unsurprisingly diverse, ranging from regulating contractile state and cellular proliferation to Ca2+ homeostasis and cellular permeability. This review will focus on emerging evidence of CaMKII as an essential component of the vascular system, with a focus on the kinase isoform/splice variants and cellular system studied.

Novel Next-Generation Sequencing and Networks-Based Therapeutic Targets: Realistic and More Effective Drug Design and Discovery

2014 ◽  
Vol 20 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Dimitrios Roukos ◽  
Giannis Baltogiannis ◽  
Christos Katsouras ◽  
Aris Bechlioulis ◽  
Katerina Naka ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Drug Design ◽  
Therapeutic Targets ◽  
Effective Drug ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Inflammatory Neuropsychiatric Disorders and COVID-19 Neuroinflammation

2021 ◽  
pp. 1-55
Author(s):  
Siu Wa Tang ◽  
Daiga Helmeste ◽  
Brian Leonard
Keyword(s):  
Immune Responses ◽  
Clinical Management ◽  
Neuronal Damage ◽  
Treatment Resistance ◽  
Neuropsychiatric Disorders ◽  
Acute Stage ◽  
Management Approach ◽  
Neuropsychiatric Diseases ◽  
Anti Inflammatory

Abstract Neuropsychiatric sequalae to COVID-19 infection are beginning to emerge, like previous Spanish influenza and SARS episodes. Streptococcal infection in pediatric patients causing OCD (PANDAS) is another recent example of an infection-based psychiatric disorder. Inflammation associated with neuropsychiatric disorders has been previously reported but there is no standard clinical management approach established. Part of the reason is that it is unclear what factors determine the specific neuronal vulnerability and the efficacy of anti-inflammatory treatment in neuroinflammation. The emerging COVID-19 data suggested that in the acute stage, wide-spread neuronal damage appears to be the result of abnormal and overactive immune responses and cytokine storm is associated with poor prognosis. It is still too early to know if there are long term specific neuronal or brain regional damages associated with COVID-19, resulting in distinct neuropsychiatric disorders. In several major psychiatric disorders where neuroinflammation is present, patients with abnormal inflammatory markers may also experience less than favorable response or treatment resistance when standard treatment is used alone. Evidence regarding the benefits of co-administered anti-inflammatory agents such as COX-2 inhibitor is encouraging in selected patients though may not benefit others. Disease modifying therapies are increasingly being applied to neuropsychiatric diseases characterized by abnormal or hyperreactive immune responses. Adjunct anti-inflammatory treatment may benefit selected patients and is definitely an important component of clinical management in the presence of neuroinflammation.

scholarly journals Assessment of tuberous sclerosis-associated neuropsychiatric disorders using the MINI-KID tool: a pediatric cohort study

2021 ◽  
Author(s):  
Yifeng Ding ◽  
Ji Wang ◽  
Hao Zhou ◽  
Taoli Li ◽  
Shuizhen Zhou ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Normal Development ◽  
Refractory Epilepsy ◽  
Neuropsychiatric Disorders ◽  
Number Of Children ◽  
Hyperactivity Disorder ◽  
Neuropsychiatric Diseases ◽  
Rapid Control ◽  
Development Group ◽  
Neuropsychiatric Illness

Abstract Background: Tuberous sclerosis-associated neuropsychiatric disorders (TANDs) have not been studied before in China. We aimed to assess the psychiatric level of TAND using the Mini International Neuropsychiatric Interview for Children (MINI-KID) in China.Results: A total of 83.16% of patients (79/95) had at least one TAND, and 70.53% (67/95) had an intellectual disability. The MINI-KID tool diagnosed a total of 16 neuropsychiatric diseases, the most common of which were attention-deficit/hyperactivity disorder (ADHD) (51.58%, 49/95) and social anxiety disorder (41.05%, 39/95). The number of children with neuropsychiatric diseases in the TSC group was significantly greater than the number in the normal development group (p <0.0001). Epilepsy before the age of 2 years, a seizure frequency of more than once a month, and the use of more than 2 antiepileptic drugs were closely associated with the occurrence of TAND.Conclusion: The MINI-KID can be used as a standardized tool to examine the psychiatric level of TANDs in children with TSC aged 6-16 years. The rate of neuropsychiatric diseases in children with TSC reached 83.16%. Early onset of epilepsy, frequent seizures, and refractory epilepsy are risk factors for TAND. Early, reasonable, and rapid control of seizures is related to reducing the risk of neuropsychiatric illness in children with epilepsy.

scholarly journals SPECIFIC MARKERS OF NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS WITH MENTAL DISORDERS – REVIEW OF THE LITERATURE

2019 ◽  
Vol 72 (7) ◽  
pp. 1359-1363
Author(s):  
Marcin Zarzycki ◽  
Magdalena Flaga-Łuczkiewicz ◽  
Joanna Czuwara ◽  
Lidia Rudnicka
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Psychiatric Disorders ◽  
Lupus Erythematosus ◽  
Neuropsychiatric Disorders ◽  
Systemic Lupus ◽  
Medical Specialties ◽  
Potential Association ◽  
Neuropsychiatric Sle ◽  
Neuropsychiatric Diseases ◽  
Wide Range

Systemic lupus erythematosus (SLE) is a chronic multiorgan autoimmune disease belonging to spectrum of interest of many medical specialties. Wide range of patients 14−75% with SLE suffers from neuropsychiatric disorders. The problematic diagnosis of neuropsychiatric SLE has generated many studies focusing on etiology of the disease with the presence of specific autoantibodies, abnormalities which can be detected by imaging examinations or correlation with catecholamine levels. The aim of this review paper is to discuss the frequency of neuropsychiatric disturbances in patients with SLE and their potential association with immunological abnormalities and specific disease markers. So far published literature regarding this topic indicates the usefulness of autoantibodies specificity. The use of the specific antibodies may be helpful in targeting diagnostics towards psychiatric disorders, especially depressive ones. Imaging scanning techniques such as computed tomography (CT) have limited value in psychiatric disorders diagnosis but can be useful in neurological symptoms and complains. Therapeutic use of systemic glucocorticosteroids due to anti-inflammatory properties with multidirectional action, may also significantly influence the course of neuropsychiatric diseases, especially in patients with SLE. Awareness of the morbidity of neuropsychiatric disorders and the possibilities of their diagnosis are important in the management of patients with systemic lupus erythematosus, which significantly affects the quality of life of patients, treatment efficacy and psyche.

scholarly journals Molybdenum Enzymes and How They Support Virulence in Pathogenic Bacteria

2020 ◽  
Vol 11 ◽  
Author(s):  
Qifeng Zhong ◽  
Bostjan Kobe ◽  
Ulrike Kappler
Keyword(s):  
Drug Targets ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogens ◽  
Energy Generation ◽  
Cellular Functions ◽  
Pathogen Fitness ◽  
Future Drug ◽  
Domains Of Life ◽  
Cofactor Biosynthesis ◽  
And Function

Mononuclear molybdoenzymes are highly versatile catalysts that occur in organisms in all domains of life, where they mediate essential cellular functions such as energy generation and detoxification reactions. Molybdoenzymes are particularly abundant in bacteria, where over 50 distinct types of enzymes have been identified to date. In bacterial pathogens, all aspects of molybdoenzyme biology such as molybdate uptake, cofactor biosynthesis, and function of the enzymes themselves, have been shown to affect fitness in the host as well as virulence. Although current studies are mostly focused on a few key pathogens such as Escherichia coli, Salmonella enterica, Campylobacter jejuni, and Mycobacterium tuberculosis, some common themes for the function and adaptation of the molybdoenzymes to pathogen environmental niches are emerging. Firstly, for many of these enzymes, their role is in supporting bacterial energy generation; and the corresponding pathogen fitness and virulence defects appear to arise from a suboptimally poised metabolic network. Secondly, all substrates converted by virulence-relevant bacterial Mo enzymes belong to classes known to be generated in the host either during inflammation or as part of the host signaling network, with some enzyme groups showing adaptation to the increased conversion of such substrates. Lastly, a specific adaptation to bacterial in-host survival is an emerging link between the regulation of molybdoenzyme expression in bacterial pathogens and the presence of immune system-generated reactive oxygen species. The prevalence of molybdoenzymes in key bacterial pathogens including ESKAPE pathogens, paired with the mounting evidence of their central roles in bacterial fitness during infection, suggest that they could be important future drug targets.

scholarly journals Genome‐wide transcriptomic and proteomic studies of Rett syndrome mouse models identify common signaling pathways and cellular functions as potential therapeutic targets

2019 ◽  
Vol 40 (12) ◽  
pp. 2184-2196 ◽  
Author(s):  
Rahul Krishnaraj ◽  
Florencia Haase ◽  
Bronte Coorey ◽  
Edward J Luca ◽  
Ingar Wong ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Rett Syndrome ◽  
Mouse Models ◽  
Therapeutic Targets ◽  
Cellular Functions ◽  
Genome Wide

More purinergic receptors deserve attention as therapeutic targets for the treatment of cardiovascular disease

2020 ◽  
Vol 319 (4) ◽  
pp. H723-H729 ◽  
Author(s):  
Bernhard Wernly ◽  
Zhichao Zhou (周稚超)
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Purinergic Receptors ◽  
Treatment Options ◽  
Experimental Studies ◽  
Therapeutic Targets ◽  
Independent Effect ◽  
Coronary Syndrome ◽  
Future Drug ◽  
New Treatment

Cardiovascular disease is a major cause of morbidity and mortality worldwide. Innovative new treatment options for this cardiovascular pandemic are urgently needed. Activation of purinergic receptors (PRs) is critically involved in the development and progression of cardiovascular disease including atherosclerosis, ischemic heart disease, hypertension, and diabetes. PRs have been targeted for the treatment of several cardiovascular diseases in a clinical setting. The P2Y12R antagonists such as clopidogrel, ticagrelor, and others are the most successful class of purinergic drugs targeting platelets for the treatment of acute coronary syndrome. In addition to targeting platelets, ticagrelor may exert P2Y12R-independent effect by targeting erythrocyte-mediated purinergic activation. The partial A1R agonist neladenoson and the A2AR agonist regadenoson have been applied in cardiovascular medicine. In experimental studies, many other PRs have been shown to play a significant role in the development and progression of cardiovascular diseases, and targeting these receptors have resulted in promising outcomes. Therefore, many of these PRs including A2BR, A3R, P2X3R, P2X4R, P2X7R, P2Y1R, P2Y4R, P2Y6R, and P2Y11R can be considered as therapeutic targets. However, the multitude of PR subtypes expressed in different cells of the cardiovascular system may constitute a challenge whether single or multiple receptors should be targeted at the same time for the best efficacy. The present review discusses the promising purinergic drugs used in clinical studies for the treatment of cardiovascular disease. We also update experimental evidence for many other PRs that can be considered as therapeutic targets for future drug development.

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