scholarly journals Homocysteine and Asymmetric Dimethylarginine (ADMA) in Neurological Diseases

2017 ◽  
Vol 6 (2) ◽  
pp. 930-939
Author(s):  
Jolanta Dorszewska
Keyword(s):  
Neurodegenerative Diseases ◽  
Metabolic Pathways ◽  
Asymmetric Dimethylarginine ◽  
Neurological Diseases ◽  
No Synthase ◽  
Lipid Lowering ◽  
Endogenous Inhibitor ◽  
Pathological Conditions ◽  
The Family ◽  
Key Factor

Homocysteine (Hcy) is formed from methionine (Met) and is distributed in two metabolic pathways: in the process of remethylation to Met and in the process of transsulfuration to cysteine. Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular and neurological diseases such as: Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and stroke. Increased Hcy level may lead to endothelial dysfunction due to impaired bioavailability of endothelium-derived nitric oxide (NO). The molecular mechanism decreasing the levels of NO in HHcy conditions is incompletely understood, but it seems that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may be a key factor. ADMA is formed from L-arginine by enzymes in the family of protein N-methyltransferases (PRMT) and may undergo hydrolysis to L-citrulline and dimethylamine with the participation of dimethylaminohydrolase (DDAH). In pathological conditions such as neurodegenerative diseases, Hcy may lead to increased ADMA concentrations by inhibiting the activity of DDAH. Several drugs, such L-dopa, antiepileptic drugs, and lipid-lowering drugs, may interfere with the metabolic pathways of thiols, leading to an alteration of plasma Hcy and ADMA levels. It seems that administration of L-arginine, in conjunction with B vitamins, to patients with HHcy may be a new method in the treatment of neurodegenerative diseases.

ADMA and hyperhomocysteinemia

2005 ◽  
Vol 10 (1_suppl) ◽  
pp. S27-S33 ◽  
Author(s):  
Sanjana Dayal ◽  
Steven R Lentz
Keyword(s):  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Asymmetric Dimethylarginine ◽  
Strong Association ◽  
No Synthase ◽  
Endogenous Inhibitor ◽  
Plasma Adma ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

Hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke. Like many other cardiovascular risk factors, hyperhomocysteinemia produces endothelial dysfunction due to impaired bioavailability of endothelium-derived nitric oxide (NO). The molecular mechanisms responsible for decreased NO bioavailabil ity in hyperhomocysteinemia are incompletely understood, but emerging evidence suggests that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may be a key mediator. Homocysteine is produced during the synthesis of ADMA and can alter ADMA metabolism by inhibiting dimethylarginine dimethy laminohydrolase (DDAH). Several animal and clinical studies have demonstrated a strong association between plasma total homocysteine, plasma ADMA, and endothelial dysfunction. These observations suggest a model in which elevation of ADMA may be a unifying mechanism for endothelial dysfunction during hyper homocysteinemia. The recent development of transgenic mice with altered ADMA metabolism should provide further mechanistic insights into the role of ADMA in hyperhomocysteinemia.

scholarly journals Asymmetric Dimethylarginine, C-Reactive Protein, and Carotid Intima-Media Thickness in End-Stage Renal Disease

2002 ◽  
Vol 13 (2) ◽  
pp. 490-496
Author(s):  
Carmine Zoccali ◽  
Francesco Antonio Benedetto ◽  
Renke Maas ◽  
Francesca Mallamaci ◽  
Giovanni Tripepi ◽  
...  
Keyword(s):  
End Stage Renal Disease ◽  
Asymmetric Dimethylarginine ◽  
Intima Media Thickness ◽  
No Synthase ◽  
Endogenous Inhibitor ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Plasma Adma ◽  
Stage Renal Disease ◽  
End Stage

ABSTRACT. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase that has been linked to endothelial dysfunction and atherosclerosis in the general population. ADMA is also elevated in end-stage renal disease and may contribute to the high cardiovascular risk in patients with chronic renal failure. A prospective cohort study was performed to investigate the relationship between plasma ADMA, C-reactive protein (CRP), and intima-media thickness (IMT) in 90 patients undergoing hemodialysis. In the baseline study, plasma ADMA was directly related to IMT both on univariate analysis (r = 0.32, P = 0.002) and on multiple regression analysis (β = 0.23, P = 0.01). In the follow-up study (15 mo) IMT changes were significantly related to ADMA (r = 0.51, P = 0.02) and serum CRP (r = 0.53, P = 0.01) in patients with initially normal IMT. In these patients, ADMA and CRP were strongly interrelated (r = 0.64, P = 0.002), and on multiple regression analysis the interaction between ADMA and CRP emerged as the sole independent predictor of the progression of intimal lesions. Independently of other risk factors, plasma ADMA in patients on hemodialysis is significantly related to IMT. Furthermore, in patients with initially normal IMT, ADMA and CRP are interacting factors in the progression of carotid intimal lesions. These data support the hypothesis that accumulation of this endogenous inhibitor of NO synthase is an important risk factor for cardiovascular disease in chronic renal failure and suggest a possible link between ADMA and inflammation.

scholarly journals The emerging role of asymmetric dimethylarginine in cardiovascular disease

2008 ◽  
Vol 14 (4) ◽  
pp. 306-314 ◽  
Author(s):  
R. N. Rodionov ◽  
I. O. Blokhin ◽  
M. M. Galagudza ◽  
E. V. Shlyakhto ◽  
S. R. Lentz
Keyword(s):  
Nitric Oxide ◽  
Risk Factor ◽  
Metabolic Pathways ◽  
Asymmetric Dimethylarginine ◽  
Structural Analog ◽  
No Synthase ◽  
No Production ◽  
Causative Role ◽  
Vascular Events

Asymmetric dimethylarginine (ADMA) is a methylated derivative of the amino acid L-arginine that is receiving increasing attention as a cardiovascular risk factor. As a structural analog of L-arginine, ADMA can inhibit the activity of nitric oxide (NO) synthase, resulting in decreased NO production in blood vessels and other tissues. While substantial epidemiological and experimental evidence links elevated levels of ADMA with endothelial dysfunction and adverse vascular events, the causative role of ADMA in cardiovascular diseases remains still largely unproven. To definitively determine whether ADMA is a biomarker or a causative risk factor, a better understanding of the biochemistry, genetics, and pharmacology of the ADMA metabolic pathways is needed.

scholarly journals Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders

2020 ◽  
Vol 13 (8) ◽  
pp. dmm045211
Author(s):  
Julia Gamache ◽  
Young Yun ◽  
Ornit Chiba-Falek
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Neurodegenerative Diseases ◽  
Late Onset ◽  
Neurological Diseases ◽  
Careful Examination ◽  
Age Related ◽  
Female Brain ◽  
Key Factor

ABSTRACTThe importance of apolipoprotein E (APOE) in late-onset Alzheimer's disease (LOAD) has been firmly established, but the mechanisms through which it exerts its pathogenic effects remain elusive. In addition, the sex-dependent effects of APOE on LOAD risk and endophenotypes have yet to be explained. In this Review, we revisit the different aspects of APOE involvement in neurodegeneration and neurological diseases, with particular attention to sex differences in the contribution of APOE to LOAD susceptibility. We discuss the role of APOE in a broader range of age-related neurodegenerative diseases, and summarize the biological factors linking APOE to sex hormones, drawing on supportive findings from rodent models to identify major mechanistic themes underlying the exacerbation of LOAD-associated neurodegeneration and pathology in the female brain. Additionally, we list sex-by-genotype interactions identified across neurodegenerative diseases, proposing APOE variants as a shared etiology for sex differences in the manifestation of these diseases. Finally, we present recent advancements in ‘omics’ technologies, which provide a new platform for more in-depth investigations of how dysregulation of this gene affects the development and progression of neurodegenerative diseases. Collectively, the evidence summarized in this Review highlights the interplay between APOE and sex as a key factor in the etiology of LOAD and other age-related neurodegenerative diseases. We emphasize the importance of careful examination of sex as a contributing factor in studying the underpinning genetics of neurodegenerative diseases in general, but particularly for LOAD.

Enterovirus D-68 Molecular Virology, Epidemiology, and Treatment: an update and way forward

2020 ◽  
Vol 20 ◽  
Author(s):  
Mahmoud Ahmed Ebada ◽  
Notila Fayed ◽  
Souad Alkanj ◽  
Ahmed Wadaa Allah
Keyword(s):  
Current Knowledge ◽  
Rna Virus ◽  
Neurological Diseases ◽  
Cross Reactivity ◽  
Serological Tests ◽  
Molecular Virology ◽  
Acute Flaccid Myelitis ◽  
The Family ◽  
Pcr Products ◽  
Enterovirus D68

: Enterovirus D68 (EV-D68) is a single-stranded positive-sense RNA virus, and it is one of the family Picornaviridae. Except for EV-D68, the family Picornaviridae has been illustrated in literature. EV-D68 was first discovered and isolated in California, USA, in 1962. EV-D68 has resulted in respiratory disorders’ outbreaks among children worldwide, and it has been detected in cases of various neurological diseases such as acute flaccid myelitis (AFM). A recent study documented a higher number of EV-D68 cases associated with AFM in Europe in 2016 compared to the 2014 outbreak. EV-D68 is mainly diagnosed by quantitative PCR, and there is an affirmative strategy for EV-D68 detection by using pan-EV PCR on the untranslated region and/or the VP1 or VP2, followed by sequencing of the PCR products. Serological tests are limited due to cross-reactivity of the antigens between the different serotypes. Many antiviral drugs for EV-D68 have been evaluated, and showed promising results. In our review, we discuss the current knowledge about EV-D68 and its role in the development of AFM.

The interaction Between Arachidonic Acid Metabolism and Homocysteine

2020 ◽  
Vol 20 ◽  
Author(s):  
Elisa Domi ◽  
Malvina Hoxha ◽  
Bianka Hoxha ◽  
Bruno Zappacosta
Keyword(s):  
Cardiovascular Disease ◽  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Neurological Diseases ◽  
Arachidonic Acid Metabolism ◽  
Epoxyeicosatrienoic Acids ◽  
Pathological Conditions ◽  
Literature Searches ◽  
Hydroxyeicosatetraenoic Acids ◽  
Improve Health

Purpose: Hyperhomocysteinemia (HHcy) has been considered a risk factor for different diseases including cardiovascular disease (CVD), inflammation, neurological diseases, cancer and many other pathological conditions. Likewise, arachidonic acid (AA) metabolism is implicated in both vascular homeostasis and inflammation as shown by the development of CVD following the imbalance of its metabolites. Aim of The Review: This review summarizes how homocysteine (Hcy) can influence the metabolism of AA. Methods: In silico literature searches were performed on PubMed and Scopus as main sources. Results: Several studies have shown that altered levels of Hcy, through AA release and metabolism, can influence the synthesis and the activity of prostaglandins (PGs), prostacyclin (PGI₂), thromboxane (TXA), epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs). Conclusions: We believe that by targeting Hcy in AA pathways, novel compounds with better pharmacological and pharmacodynamics benefits may be obtained and that this information is valuable for dietician to manipulate diets to improve health.

scholarly journals Roles of Microglial Ion Channel in Neurodegenerative Diseases

2021 ◽  
Vol 10 (6) ◽  
pp. 1239
Author(s):  
Alexandru Cojocaru ◽  
Emilia Burada ◽  
Adrian-Tudor Bălșeanu ◽  
Alexandru-Florian Deftu ◽  
Bogdan Cătălin ◽  
...  
Keyword(s):  
Ion Channels ◽  
Neurodegenerative Diseases ◽  
Excitable Cells ◽  
Proton Channels ◽  
Voltage Gated ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
The Common ◽  
Transient Receptor ◽  
The Impact

As the average age and life expectancy increases, the incidence of both acute and chronic central nervous system (CNS) pathologies will increase. Understanding mechanisms underlying neuroinflammation as the common feature of any neurodegenerative pathology, we can exploit the pharmacology of cell specific ion channels to improve the outcome of many CNS diseases. As the main cellular player of neuroinflammation, microglia play a central role in this process. Although microglia are considered non-excitable cells, they express a variety of ion channels under both physiological and pathological conditions that seem to be involved in a plethora of cellular processes. Here, we discuss the impact of modulating microglia voltage-gated, potential transient receptor, chloride and proton channels on microglial proliferation, migration, and phagocytosis in neurodegenerative diseases.

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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