China
Africa
Explore chapters and articles related to this topic
Cardiac Hypertrophy, Heart Failure and Cardiomyopathy
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
These diseases lead to cardiac hypertrophy and include Pompe's disease. Myocyte vacuoles containing glycogen or intermediary metabolites occur (Fig. 5.79). The glycogen is brightly periodic-acid Schiff (PAS) positive. The heart often enlarges with a thick-walled asymmetric left ventricle. Other genetic causes of cardiac hypertrophy include mutations in PRKAG2, the regulatory γ subunit of AMP-activated protein kinase. PRKAG2 mutations cause myocyte hypertrophy by stimulating glycogen-filled vacuoles but cause neither myocyte disarray nor interstitial fibrosis, which typically occur with defects of sarcomere-protein genes. Danon disease (an X-linked lysosome-associated membrane protein [LAMP2] deficiency) and Fabry's give a similar appearance both macroscopically and microscopically. Cardiomyopathy due to PRKAG2 mutations with progressive conduction-system disease may necessitate the implantation of a pacemaker but has a good long-term prognosis. By contrast, the prognosis associated with cardiomyopathy due to LAMP2 mutations is poor with onset of disease during adolescence, followed by a rapid progression towards end-stage HF early in adulthood.
Improvement of Cognitive Function in Patients with Alzheimer’s Disease using Ketogenic Diets
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Diet-induced ketosis was reported to upregulate GLUT1 as well as monocarboxylate transporters in rat brains, which may increase the utilization of not only ketone bodies but also glucose in the brain (Puchowicz et al. 2007). In-vitro studies demonstrated that β-hydroxybutyric acid protected hippocampal cells from β-amyloid-induced toxicity. β-Amyloid activates mitochondrial protein kinases, which inactivate the pyruvate dehydrogenase complex by phosphorylation. It is possible that β-hydroxybutyric acid bypasses a block at mitochondrial pyruvate dehydrogenase and supplies substrates for the TCA cycle, which helps maintain mitochondrial function (Kashiwaya et al. 2000). β-Hydroxybutyric acid has been demonstrated to act as an agonist to G-protein coupling receptor (GPR)-109A, which is expressed on glial cells and suppresses inflammation (Fu et al. 2015). These biological functions of ketone bodies beyond energy source may be involved in the improvement in cognitive function of patients with AD via ketogenic diets. A better understanding of these mechanisms would contribute to the development of more efficient management and therapies for AD.
Chemokine Receptors in the Brain: Hierarchical Expression by Subsets of Neurons
Published in Richard Horuk, Chemoattractant Ligands and Their Receptors, 2020
Stephen C. Peiper, Richard Horuk
The association of IL-8RB with the neuritic component of Alzheimer’s disease provides further rationale to postulate that IL-8 and/or MGSA may promote regenerative responses in neurons. It is evident that Alzheimer’s disease is a complex disorder which involves multiple reparative mechanisms (see References 56 and 57 for reviews) and may be associated with genetic mutations in the gene encoding the amyloid precursor polypeptide on chromosome 21 and genes encoding polypeptides predicted to contain seven transmembrane spanning helices on chromosomes 1 and 14. Alzheimer’s plaques have been found to contain multiple protein kinases and phosphoproteins, as well as hyperphosphorylated intermediate filaments, perhaps representing ongoing signal transduction involved in neuritic outgrowth. The induction of IL-8RB expression may indicate the involvement of the cognate chemokines in regenerative and reparative mechanisms in the central nervous system.
Identification of a new structural family of SGK1 inhibitors as potential neuroprotective agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Ines Maestro, Enrique Madruga, Patricia Boya, Ana Martínez
Protein kinases are responsible for modulating the activity of other downstream proteins by means of their phosphorylation of specific residues like serine, threonine or tyrosine. They are found in important cellular processes, like cell proliferation, apoptosis, neuroinflammation and other cell signalling pathways. Pathological imbalance of these protein kinases has been reported in several pathologies, including neurodegenerative diseases. Thus, they have become a perfect target to develop a drug discovery program in order to find new compounds to modulate them6,7. In fact, in December 2021 there were 68 protein kinase inhibitors approved by the FDA, most of them with oncology purposes8. However, none of them are directed to neurodegenerative diseases, which are everyday more prevalent in the society due to the increase in life expectancy.
Jing-an oral liquid alleviates Tourette syndrome via the NMDAR/MAPK/CREB pathway in vivo and in vitro
Published in Pharmaceutical Biology, 2022
Leying Xi, Xixi Ji, Wenxiu Ji, Yue’e Yang, Yajie Zhang, Hongyan Long
Microglia are innate immune effector cells in the brain that play a crucial role in physiological processes in the central nervous system (CNS) (Arcuri et al. 2017). It has been found that there is a correlation between the state of microglia and the occurrence of TS. Moreover, it has been reported that the expression of microglia transporter proteins in the bilateral caudate nucleus is increased in children with TS (Kumar et al. 2015). Additionally, an analysis of the autopsy reports for TS patients reveals an increased number of CD45+ expressing microglia cells in striatal areas of the basal ganglia (Lennington et al. 2016). Over-activated microglia cells produce reactive oxygen species, inflammatory cytokines, chemokines, and Glu (Takeuchi and Suzumura 2014). The release of excitatory amino acids by microglia is a key mediator of excitotoxic damage. Microglia cells express various Glu receptors (GluRs); however, the N-methyl-d-aspartate receptor (NMDAR) is crucial for the activity of Glu. Unfortunately, the relationship between NMDAR and signaling mechanisms in TS is unknown. Recent evidence suggests that mitogen-activated protein kinase (MAPK) plays a critical role in regulating the neurochemical and pathophysiological properties of NMDAR (Haddad 2005). As one of the downstream targets of MAPK signaling, cyclic AMP response element-binding protein (CREB) can be phosphorylated. Moreover, MAPK signaling, in the presence of excitatory neurotransmitters and stress is involved in the development of CNS diseases (Koga et al. 2019).
S-Propargyl-cysteine prevents concanavalin A-induced immunological liver injury in mice
Published in Pharmaceutical Biology, 2022
Beilei Ma, Yicheng Mao, Lingling Chang, Tao Dai, Xiaoming Xin, Fenfen Ma, Zhijun Wang, Zhuqing Shen, Qibing Mei, Yizhun Zhu
Previous studies have established that the release of inflammatory cytokines leads to liver injury after the Con A injection. The mitogen-activated protein kinase (MAPK) signalling pathway has previously been described to regulate the production of inflammatory cytokines. In this pathway, activation of c-Jun N-terminal kinase (JNK) and protein kinase B (Akt) has been reported to play an important role in hepatitis and determine the fate of the hepatocytes (death or survival). In this study, western blot analysis of phosphorylated JNK (p-JNK) and phosphorylated Akt (p-Akt) revealed increased expressions of these proteins in the livers of mice intoxicated with Con A after 12 h. On the contrary, SPRC (10 mg/kg) administration reduced the expressions of p-JNK (p < 0.01 vs. Con A) and p-Akt (p < 0.05 vs. Con A). This result indicated that SPRC pre-treatment suppressed the activation of the MAPK pathway (Figure 4). However, this suppression was reversed by the CSE inhibitor PAG.