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Medicinal Plants for Eczema
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Once Complex I has formed, inhibitors of nuclear factor kappa B (IκB) become phosphorylated and dissociate from nuclear factor kappa B (NF-κB) transcription factors. This allows NF-κB to become active and translocate into the nucleus (Miller et al., 2010). Inside the nucleus, NF-κB transcribes sections of the DNA that are required to activate the synthesis of cytokines and chemokines such as TNF-α, IL-1β, IL-6, IL-8 and IFN-γ (Palladino et al., 2003). If IκB is unable to dissociate from NF-κB, the TNFR1 intracellular domain, known as the death domain, recruits a cytoplasmic complex, Complex II, which is comprised of RIP1 or TRADD and Fas-associated protein with death domain (FADD). Once formed, FADD recruits caspase 8 or 10 that are activated upon self-cleavage and cause a protease cascade which results in apoptosis (Xu and Shi, 2007). To prevent this, active NF-κB transcribes inhibitors of apoptosis proteins (IAP) such as X-chromosome-linked IAP (XIAP), which bind to and inhibit active caspases (Van Antwerp et al., 1998).
Autoimmune Lymphoproliferative Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Subsequent characterization of several ALPS-associated genes (e.g., FAS, FASLG, CASP10) revealed valuable insights into the molecular pathogenesis of ALPS and ALPS-related disorders. Under normal circumstances, interaction between FAS and FAS ligand activates the FAS-associated death domain (FADD) protein and triggers the caspase cascade, leading to cellular apoptosis. However, germline or somatic mutations in FAS, FASLG, and CASP10 (which participates in the formation of death-inducing signaling complex comprising FADD, caspase-8, and caspase-10) cause defects in RAS-mediated apoptosis and thus increase lymphocyte accumulation and autoimmune reactivity [4,5].
Apoptosis and Cell Death
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
In apoptosis signalling, receptor trimerization leads to recruitment of FADD (Fas-associated death domain), which binds the intracellular death domain (DD) portion of Fas, and procaspase 8 molecules bind to the death effector domain (DED) of FADD (Figure 6.2). Hence, procaspase 8 molecules are clustered and activated by autocleavage on a platform known as the death inducing signal complex (DISC). Trimerized receptors may also cluster into receptor microaggregates. In some cell types (type I cells), caspase 8 activation at the DISC is sufficient for downstream effector procaspase cleavage, but in many cell types (type II cells), the mitochondrial pathway is engaged to amplify the death signal by caspase 8-dependent cleavage of the BH3-only protein Bid, converting it to a form that is able to transmit the apoptotic signal to the mitochondrion. In addition, cytotoxic T cells release perforin, which penetrates the epithelial cell membrane, and granzyme B, a serine protease that can cleave and activate Bid, hence engaging the mitochondrial pathway.
Serum Fas levels during first week of sepsis are associated with severity and mortality
Published in Expert Review of Molecular Diagnostics, 2023
Leonardo Lorente, María M. Martín, Raquel Ortiz-López, Agustín F. González-Rivero, Adriana González-Mesa, Jacobo J. Villacampa-Jiménez, Alejandro Jiménez, Antonia Pérez-Cejas
Fas-mediated apoptosis contributes to different physiological and pathological cellular processes. Fas signaling has dual apoptotic and non-apoptotic pathways in different cells that contribute to beneficial (homeostasis of peripheral T cells) and detrimental (development of autoimmune diseases) effects [5–7]. There are two types of FasL, membrane-bound FasL (mFasL) and soluble FasL (sFasL), with different effects with respect to apoptosis. On the one hand, mFasL leads to the recruitment of Fas-associated protein with death domain (FADD) promoting the activation of apoptosis. On the other hand, sFasL activates extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) promoting apoptotic inhibition [5–7]. Another relevant point is the possibility that sFas binds to sFasL and that non-binding to mFasL prevents apoptosis signaling [5–7].
Repurposing Natural Dietary Flavonoids in the Modulation of Cancer Tumorigenesis: Decrypting the Molecular Targets of Naringenin, Hesperetin and Myricetin
Published in Nutrition and Cancer, 2022
Carolina Sousa, Denise Duarte, Beatriz Silva-Lima, Mafalda Videira
Within the variety of cell biological features needed to generate hyperplasic cells, breaking down apoptosis is critical to start the tumorigenic process (93). It can be initiated by intrinsic and extrinsic stimuli, with the intervention of two major family proteins – caspases and Bcl-2 (B-cell lymphoma 2). The extrinsic pathway of apoptosis is initiated when a death ligand binds to a death receptor (eg., TNF-α, Fas and DR5). Together with adapter proteins (FADD - Fas-associated death domain protein - or TRADD) recruit and activate caspase-8 and −10. Once activated they can either activate caspase-3/6 and −7 or initiate the intrinsic apoptotic pathway by cleavage of BID. The latter can also be initiated by endogenous stimuli, such as oxidative stress. At this point, the pro-apoptotic Bcl-2 family proteins (Bax, Bid and Bak) permeabilize the outer mitochondrial membrane, leading to the efflux of cytochrome c to the cytosol, and binds to Apaf-1 to recruit and activate caspase-9. Both stimuli result in activation of caspase-3 and activate the “execution pathway” of apoptosis. Activation of caspase-3 results in activation of PARP ((Poly(ADP-ribose) polymerase)-1) (94, 95).
Protein Kinase C-Delta Defect in Autoimmune Lymphoproliferative Syndrome-Like Disease: First Case from the National Iranian Registry and Review of the Literature
Published in Immunological Investigations, 2022
Niusha Sharifinejad, Gholamreza Azizi, Nasrin Behniafard, Majid Zaki-Dizaji, Mahnaz Jamee, Reza Yazdani, Hassan Abolhassani, Asghar Aghamohammadi
Autoimmune lymphoproliferative syndrome (ALPS) is an inherited lymphoproliferative disorder caused by mutations in genes within the apoptotic signaling pathway mediated by the first apoptosis signal (FAS), which plays central role in lymphocyte homeostasis (Puck and Sneller 1997). Although most of ALPS patients harbor mutations in FAS gene, mutations in other genes associated with the FAS signaling pathway including FAS ligand, Caspase 8, Caspase 10, and FADD are classified as typical ALPS. Moreover, pathogenic variants in genes outside the FAS pathway have been reported in association with clinical findings similar to ALPS. However, they either do not fulfill the current diagnostic criteria of ALPS or have other distinct phenotypes, therefore are listed as ALPS-like disorders. These disorders include defect in the lipopolysaccharide responsive beige-like anchor protein (LRBA), cytotoxic T-lymphocyte associated protein 4 (CTLA4), KRAS proto-oncogene, Magnesium transporter 1 (MAGT1), NRAS proto-oncogene, Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) and signal transducer and activator of transcription 3 (STAT3) (Bousfiha et al. 2020).