Role of Tandem Mass Spectrometry in Diagnosis and Management of Inborn Errors of Metabolism
P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas in Advanced Studies in Experimental and Clinical Medicine, 2021
The levels of expression of mitochondrial matrix proteins including isovaleryl coenzyme A dehydrogenase, agmatinase, and cytochrome b5 were downregulated in early stages of Wilson’s disease. As mitochondrial injuries progressed, expression levels of malate dehydrogenase 1, annexin A5, S-adenosylhomocysteine hydrolase, transferrin, and sulfite oxidase 1 were differentially regulated. S-adenosylhomocysteine hydrolase was under-expressed and is hypothesized to play a role in neurological pathology of Wilson’s disease. The study was done on a mouse model of Wilson’s disease (LEC rats) [57]. Shotgun proteomic analysis of Atp7b(-/-) mouse model of Wilson’s disease revealed increased expression of DNA repair machinery and nucleus-localized glutathione peroxidase (SeIH), and reduced expression ofligand-activated nuclear receptors FXR/NR1H4 and GR/NR3C1 and nuclear receptor-interacting partners [58]. Remodeling of RNA processing machinery may be involved in the pathogenesis of Wilson’s disease [59].
Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats
Published in Psychiatry and Clinical Psychopharmacology, 2018
Gokhan Unal, Alpay Ates, Feyza Aricioglu
Agmatine, an endogenous amine, which is formed by decarboxylation of l-arginine, synthesized by arginine decarboxylase, and degraded by agmatinase. It is widely distributed in the body including brain and interacts with a number of receptors, alpha-adrenergic and imidazoline receptors; blocks nicotinic cholinergic, serotoninergic 5-HT3, and glutamatergic NMDA receptors; and inhibits nitric oxide synthase. Agmatine can be defined as a putative neurotransmitter/neuromodulator [16–19]. Our research group and others have demonstrated that exogenously administered agmatine has a variety of pharmacological effects related with central nervous system, such as nociception, neuroinjury/neuroprotection, cognition, epilepsy, opioid tolerance/dependence, stress, anxiety, depression, and schizophrenia. Thus, agmatine can be a new candidate of novel therapeutic target by further revealing the underlying molecular mechanisms in related physiological and pathological conditions [20–27].
Agmatine as a potential therapeutic intervention in bipolar depression: the preclinical landscape
Published in Expert Opinion on Therapeutic Targets, 2019
Devon Watts, Bianca Pfaffenseller, Bianca Wollenhaupt-Aguiar, Luiza Paul Géa, Taiane De Azevedo Cardoso, Flavio Kapczinski
In humans, recent post-mortem evidence has shown that individuals who committed suicide exhibited lower concentrations of agmatine in the cortex, specifically in Brodmann areas 4, 11, and 44, regardless of MDD diagnosis [55]. Similarly, previous literature has repeatedly linked the gene coding for human agmatinase, an enzyme which inactivates endogenous agmatine, in both BD and MDD [31]. Additionally, the number and density of agmatinase-immunopositive cell bodies in both cerebral hemispheres are strongly elevated among depressive patients, relative to controls. Moreover, patients with BD show significant elevations in agmatinase-expressing hippocampal interneurons, relative to both patients with MDD and healthy controls [88]. According to gathered evidence, the lack of agmatine or its inactivation by increased agmatinase activity may play a crucial role in the pathophysiology of depression and reveal an important target for new therapeutic approaches.
Evaluation of plasma agmatine level and its metabolic pathway in patients with bipolar disorder during manic episode and remission period
Published in International Journal of Psychiatry in Clinical Practice, 2019
Emine Yılmaz, M. Ramazan Şekeroğlu, Ekrem Yılmaz, Erdem Çokluk
The study has a number of limitations: The number of participants in the study could be increased. Agmatinase gene expression could have been helpful in determining the cause of agmatine level changes. In addition, studies performed on individuals with bipolar risk factors may be helpful in observing how agmatine levels may be affected by process changes. And also there are limited studies in the literature to explain the medication effects on agmatine levels or agmatine pathway.