China
Africa
Explore chapters and articles related to this topic
Cognition Enhancers
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Ramneek Kaur, Rashi Rajput, Sachin Kumar, Harleen Kaur, R. Rachana, Manisha Singh
If a neuron is stressed or injured, it might undergo apoptosis. It may be either extrinsic (which can be started by activating the receptors of cell surface) or intrinsic (involving the ER and the mitochondria). Cell death can be triggered by either of the losses of factors responsible for cell survival. Further, damage of DNA, which may thereby, cause the pro-apoptotic proteins from the mitochondria to stimulate caspase proteases and eventually, caspase activated DNase. Apoptosis can also be induced in caspase independent manner by triggering apoptosis-inducing factor (AIF) which is protein present in the intermembrane of the mitochondria. Attenuation of cell death can be triggered by stimulation of PKCγ in the hippocampus. Therefore, it is suggested that the activators of PKCγ inhibits apoptosis (Sun et al., 2009), thereby, increasing the usefulness as CE that can act on the patients specifically suffering from stroke, brain injury, and acute radiation sickness.
N-Acetylcysteine and Safranal prevented the brain damage induced by hyperthyroidism in adult male rats
Published in Nutritional Neuroscience, 2022
Asmaa S. Shahat, Wafaa A. Hassan, Wael M. El-Sayed
If the cells are severely damaged and the cellular architecture is lost, cells may go through apoptosis. Mitochondria contain several apoptogenic proteins in the inter-membrane space. Cytochrome c is a key mediator of apoptosis; its efflux into cytosol initiates the formation of apoptosome and activates the initiator Caspase-9 with subsequent activation of death-inducing Caspase-3. The increase in pro-apoptotic markers in the current study may be attributed to the imbalance between pro- and anti-oxidants induced by hyperthyroidism. Increase in the levels of oxidants led to oxidation of proteins and DNA and LPO, cell dysfunction and eventually cell death. Caspases stimulated by ROS may induce further free radicals release from mitochondria during the beginning of apoptosis propagating further damage. Activation of Caspase-3 induces Caspase-activated DNase (CAD) endonuclease that degrades DNA within the nucleus and initiates chromatin condensation leading to DNA fragmentation [45]. The fragmentation of DNA is now considered an important factor in the etiology of many neurodegenerative diseases. In the present study and also in other studies [44, 45], the induction of hyperthyroidism caused a significant brain DNA damage as an end result of increased apoptosis.
Chemotherapeutic and prophylactic antimalarial drugs induce cell death through mitochondrial-mediated apoptosis in murine models
Published in Drug and Chemical Toxicology, 2021
John Oludele Olanlokun, Folashade Abimbola Balogun, Olufunso Olabode Olorunsogo
The DNA fragmentation is observed as a mechanism of cell death in malaria-infected mice. We observed also that treatment with antimalarial drug (PRG) also caused DNA fragmentation and caspases 3 and 9 activation in vivo. Activation of caspases 9 and 3, which are initiator and executioner caspases, respectively, heralds the onset of apoptosis. Sequentially, degradation of nuclear DNA by caspase-activated DNA, specifically caspase 3, is one of the features of apoptotic cell death. The mechanistic, degradative cleavage of chromosomal DNA is carried out by caspase-activated DNase (CAD) that is found regulatorily complexed with inhibitor of CAD (ICAD). Signals such as oxidative stress from malarial infection or drugs (in this case ART and PRG) could induce apoptosis in such a way that activated caspase 3 could cleave ICAD and CAD could cleave chromosomal DNA for apoptosis to take place (Nagata 2000). Although it has been reported previously that liver stage of malaria parasite inhibits hepatocyte apoptosis (van de Sand et al. 2005), our results have shown that direct effects of increased DNA fragmentation, enhanced mitochondrial ATPase activity and reduced GSH level coupled with the indirect effect of oxidative stress that may occur in heme metabolism may be responsible for apoptosis in the hepatocytes.
CD133: beyond a cancer stem cell biomarker
Published in Journal of Drug Targeting, 2019
Amir Barzegar Behrooz, Amir Syahir, Syahida Ahmad
In contrast, FLIP inhibits FADD, and as a result, active caspase 8 is not produced [115]. Caspases are inactive cysteine proteins in the cytoplasm that turn into an active form by losing their aspartate. They are divided into two groups of initiating caspases (2, 8, 9, 10) and functional caspases (3, 6, 7). Functional caspases are proteolytic that have cytosolic and nuclear targets [119]. Including their cytosolic targets gelsolin, which, if cleavage by caspases, causes the breakdown of actin filaments and ultimately cell destruction. Their nuclear targets are inhibitor of caspase-activated DNase (ICAD), which connects typically to caspase-activated DNase (CAD) and disables it. Functional caspases with the release of CAD into the nucleus, destroy DNA [120]. Besides, caspase 8 converts Bid to truncated Bid (tBid) and then, proteins tBid, p53, Noxa, Puma and Bax together form the pore-forming proteins complex in the mitochondrial outer membrane. With the release of cytochrome C and apoptosome formation, activated-caspase 9 is produced and pro-caspase 3, 6, 7 converted to activated-caspase 3, 6, 7 [121]. When caspase 8 is not created, this disrupts the intrinsic apoptosis pathway. The result of these events is an increase in cancer cell invasion. Park et al. studies showed that we could consider the interaction of CD133-p53 as a new strategy to target CSCs. Their results demonstrated that P53 is one of the leading obstacles in the formation of CSCs and suppressing of CD133 by p53 leads to a reduction in the expression of stemness genes (SOX2, c-MYC, NANOG and OCT4) [103,122]. (Figure 7)