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Neurobiology of Mood Disorders
Published in Dr. Ather Muneer, Mood Disorders, 2018
Another measure of cellular metabolism is the ratio of AMP and ATP. An important sensor of the AMP/ATP ratio is adenosine monophosphate-dependent protein kinase (AMPK) which is activated upon binding to AMP. AMPK is stimulated in neurons in response to metabolic or ischemic stressors and elicits compensatory responses. AMPK phosphorylates casein kinase 1 epsilon which enhances phosphorylation of PER2, again directly pairing cellular metabolism to the circadian system.40 Moreover, the mitochondrial biogenesis stimulator, “peroxisome proliferator-activated receptor gamma coactivator 1-α”, directly regulates expression of BMAL1 and Rev-erbα and is necessary for circadian pacemaker function.41 The eventual results of metabolic dysfunction in neurons are oxidative stress, generation of reactive oxygen species and apoptosis. Therefore, given the close link between the circadian system and redox signaling, it seems reasonable to speculate that circadian rhythm disruption might lead to the accumulation of damaging free radicals and enhanced neuronal apoptosis. In fact the apoptotic genes, Wnt10, β-catenin, Dishevelled2 and transcription factor 3 promoters, are all bound by BMAL1, and Wnt pathway signaling is attenuated when BMAL1 levels are reduced. Aberrant Wnt and GSK3 signaling is implicated in mood disorders and there is emerging evidence to demonstrate that the circadian system is intimately involved in the regulation of these pathways.42
Neurological Activities of Seaweeds and their Extracts
Published in Leonel Pereira, Therapeutic and Nutritional Uses of Algae, 2018
Tau is a microtubule-associated protein (MAP) found in axons, and this protein is responsible for regulating the stability of microtubules (Goedert et al. 1988, Drechsel et al. 1992, Hirokawa et al. 1996). Hyper-phosphorylation of tau results in its dissociation from microtubules and aggregation in the form of neurofibrillary tangles (Avila et al. 2006). Hyper-phosphorylated tau protein is a major component in neurofibrillary tangles, which is a hallmark of Alzheimer’s disease, and dysregulation of kinases and phosphatases has been found to increase tau hyper-phosphorylation levels (Selkoe 1997, Hanger et al. 2009). Only three compounds (Spiralisone A, B, and Chromone 6) from seaweed have kinase inhibitory activity, and these compounds have been isolated from brown algae (Phaeophyceae). Besides, these compounds were isolated from a single species, Zonaria spiralis, collected in Australia, and all of them are phloroglucinols. The most active compound is spiralisone B, inhibiting the kinases-cyclin-dependent kinase 5 (CDK5/p25), casein kinase 1 (CK15), and glycogen synthase kinase 3 beta (GSK3ß), with IC50 values of 3, 5, and 5.4 μΜ, respectively (Zhang et al. 2012c).
Protein Phosphorylation
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
The casein kinases I and II are serine/threonine kinases with an important role in signal transduction mechanisms.513 The casein kinases can recognize specific sequences in endogenous and exogenous substrates, including src-related sequences present in some cellular polypeptides.514 The casein kinase I recognizes residues located on the carboxyl-terminal edge of acidic stretches. The enzyme phosphorylates the 25-kDa mRNA cap-binding protein.515 Phosphotyrosyl-containing side chains can act as specificity determinants for casein kinase II. Some oncoproteins are phosphorylated on serine/threonine by casein kinase II, including the c-Erb-A/thyroid hormone receptor.516 Both casein kinase II and the ribosomal protein S6 kinase are two important elements in the kinase cascade that leads to the initiation of cell proliferation stimulated by mitogens, hormones, and growth factors. Casein kinase activity may be regulated by phosphorylation. The cell cycle-associated protein kinase cdc2 catalyzes the phosphorylation of casein kinase II in vitro and at mitosis.517
Choroid plexus and CSF: an updated review
Published in British Journal of Neurosurgery, 2022
Dana Hutton, Mohammed Gadoora Fadelalla, Avinash Kumar Kanodia, Kismet Hossain-Ibrahim
Circadian rhythms control various physiological functions, such as hormone secretion, blood pressure and body temperature regulation.37 The suprachiasmatic nucleus (SCN) is deemed the ‘master clock’ of these rhythms. Its action is influenced by other ‘peripheral clocks’, termed circadian oscillators. Yamaguchi et al. proposed the ChP is functional as an intrinsic oscillator, and can influence the SCN. The group observed the rPer1*, rPer2** and rBmal1*** expression in the ChP of the lateral and fourth ventricles of male rats to be of a circadian manner. This pattern of expression is seen in the SCN and the pineal gland (PG)-regions known to exhibit circadian oscillator function.37 Interaction between the ChP, PG and SCN (intrinsic oscillators) is thought to maintain a stable 24hr circadian rhythm. The ChP was found to have a short intrinsic circadian period (∼21hrs). The authors were unable to explain this, but casein kinase I ε/δ is thought to play some role.37 Further studies are required to address this.
Unveiling Taenia solium kinome profile and its potential for new therapeutic targets
Published in Expert Review of Proteomics, 2020
Naina Arora, Anand Raj, Farhan Anjum, Rimanpreet Kaur, Suraj Singh Rawat, Rajiv Kumar, Shweta Tripathi, Gagandeep Singh, Amit Prasad
It is the largest group of kinases present in T. solium and was a consistent observation in C. elegans and Schistosoma. CMGC protein kinases are involved in embryo development, cell fate determination, Wnt signaling, MAPK signaling, and cell proliferation (supplementary 2) [34,35]. This group consists of nine families of which we found that seven are present in T. solium. These are CDK (Cyclin-dependent kinase), MAPK, GSK (glycogen synthase kinase), CDKL (CDK-like kinase), DYRK (Dual specificity Tyrosine Regulated Kinase), CK2 (Cell kinase 2/casein kinase 2), and SRPK (SR-rich protein kinase). The CLK and RCK were not present. MAPK is the most extensively studied signaling pathway that is activated in response to a stress stimulus and which leads to apoptosis and inflammation. T. solium does not have all the members of the MAPK family, but has conserved single representor of ERK1, ERK7, nmo, p38, and JNK. The CMGC kinases withhold the potential for experimental interventions as these kinases are indispensable for parasite biology in terms of regulated growth, stress response, and cellularity. The GSK kinases have been alluded in the number of diseases as potential therapeutic targets. They regulate many intracellular pathways and glucose regulation is one such pathway. The adult tapeworm inside the human host derives its nutrition from glucose, thus marking GSK as a potential entry point for interventions. Taking into consideration the conserved nature of kinases, GSK has been demonstrated as a potential drug target for Schistosoma [36].
Recent advances in modulators of circadian rhythms: an update and perspective
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Shenzhen Huang, Xinwei Jiao, Dingli Lu, Xiaoting Pei, Di Qi, Zhijie Li
Casein kinase 1 (CK1). The casein kinase family comprises seven distinct genes encoding CK1 isoforms (α, α2, γ1, γ2, γ3, δ, and ε) in mammals113. CK1δ and CK1ε have been discovered to regulate the circadian clock, and their substrates are proved to be PER1, PER2, BMAL1, and CRYs114. CK1ε-selective inhibitor compound 53 can increase in period length, leading to about 1.2-h in synchronised Rat-1 (mPer1::luc) cells115. Afterward, compounds 54–60 (Table 4 and Figure 7) were also proven to lengthen the period in cultured cells and were reviewed in other papers 49,116. Recently, compound 61 was identified as a regulator to increase period length in mammalian cells and larval zebrafish assay117. Compound 62 lengthens the period through CK1 inhibition118. All these studies reveal that the role of CK1 is important in the regulation of circadian rhythm119.