China
Africa
Explore chapters and articles related to this topic
Intracellular Redox Status and Disease Development: An Overview of the Dynamics of Metabolic Orchestra
Published in Jyoti Ranjan Rout, Rout George Kerry, Abinash Dutta, Biotechnological Advances for Microbiology, Molecular Biology, and Nanotechnology, 2022
Sharmi Mukherjee, Anindita Chakraborty
In ALS, oxidative stress induces mtDNA mutations, gliosis, and aggregation of mutant and wild-type SOD1. In 5% of cases, mutations in the SOD1 gene are associated with ALS development. Mutant SOD1 causes dysregulation of signaling molecules in motor neurons and regulates the activity of glial cells. Increased ROS levels from damaged motor neurons cause a hindrance to glutamate uptake into astrocytes, elevating extracellular glutamate levels, and excitotoxicity (Shichiri et al., 2014). ROS also activates glial cells leading to the release of further ROS/RNS and proinflammatory cytokines and inhibition of IGF-I/AKT neuroprotective pathway resulting in neurodegeneration (Liu et al., 2017; Radi et al., 2014). Redoxosomes are also known to regulate proinflammatory signals via NF-κB modulation (Li et al., 2011; Liu et al., 2017). Oxidative stress-induced mitochondrial alterations in the Purkinje cells characterize spinocerebellar ataxia (Liu et al., 2017; Stucki et al., 2016).
Gene Therapy and Gene Correction
Published in Yashwant V. Pathak, Gene Delivery Systems, 2022
Manish P. Patel, Sagar A. Popat, Jayvadan K. Patel
Many transgenic mouse models have been created by genetic engineering which express the same activity as humans with a neuron disorder. One model was developed with mice overexpressing mutant superoxide dismutase [Cu-Zn] SOD1. The main function of SOD1 is to destroy free radicals in the body—its mutation has been shown to cause Lou Gehrig’s disease, which weakens the muscles and causes physical deformation (Rosen et al. 1993; Wong et al. 1998; Morrison et al. 1998). Inserting parvalbumin in the brain of mutant SOD1 transgenic mice resulted in the delayed onset of motor neuron damage (Beers et al. 2001).
Lysosomal Storage Disorders and Enzyme Replacement Therapy
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
As reported by Nakasone et al. (2014), adenovirus-mediated expression of heat shock protein 70 (Hsp70) or treatment with an HSP-inducer geranylgeranylacetone (GGA) also increased the level of the mutant protein in human fibroblasts with the I1061T mutation in NPC1. Kirkegaard and colleagues (2016, 2010) demonstrated that treatment with the recombinant natural chaperone Hsp70 inhibited glycosphingolipid accumulation in murine models of Fabry disease, Sandhoff disease, and Niemann-Pick disease type C and attenuated neurological symptoms associated with Sandhoff and NP disease type C; the effect relies on binding to the endolysosomal anionic phospholipid bis-(monoacylglycero)phosphate (BMP), an essential co-factor for lysosomal sphingomyelin metabolism. The molecular chaperone also interacts with ASM resulting in mutual activation of ASM and Hsp70 (Zhu et al., 2014). In addition, arimoclomol, a coinducer of HSPs that is currently in clinical trials for Niemann-Pick disease type C, is an experimental drug developed by CytRx Corporation (Los Angeles, California). Worldwide rights to arimoclomol were then bought by the Danish biotech company Orphazyme ApS. Meanwhile this small molecule drug has been granted orphan drug, fast track, and rare pediatric disease designations by the FDA. The results of a recent study published by Benatar et al. (2018) further revealed that arimoclomol may be of use as a therapeutic for SOD1 amyotrophic lateral sclerosis (ALS; inheritance is possible autosomal dominant, autosomal recessive or X-linked). Cases of hereditary ALS have been attributed to mutations in a variety of different genes of which the gene encoding CuZn-superoxide dismutase (SOD1) belongs to the most common ones (Andersen and Al-Chalabi, 2011; Al-Chalabi et al., 2014).
The effects of thymoquinone on DNA damage, apoptosis and oxidative stress in an osteoblast cell line exposed to ionizing radiation
Published in Radiation Effects and Defects in Solids, 2021
Osman Yılmaz, Veysel Yüksek, Sedat Çetin, Semiha Dede, Taylan Tuğrul
IR leads to cell death due to the damage it induces on the DNA. As a result of this, the functioning of the cellular metabolism is disrupted, and cellular ageing, different levels of molecular destruction and tissue and cell damage in organs most of which have vital significance occur (4,26). Apoptosis, which is also known as programmed cell death, involves highly complicated molecular cascade events. In whether or not a cell will go into apoptosis or necrosis, the types of various harmful stimulants such as radiation, temperature, hypoxia and drugs with cytotoxic effects are highly important. While the Caspase-3, Caspase-8 and Caspase-9 genes are proteins that are effective in the apoptotic pathway, it is known that the Bcl-2 gene is one of the apoptosis-regulating proteins (27). Moreover, the production and detoxification of free radicals that are formed as a result of IR are controlled with a highly sensitive balance. As long as the balance between the formation speed and elimination speed of these molecules is not disrupted, the cell is not affected by these procedures. When this balance is disrupted in cases where oxidants increase, or antioxidants fall short, oxidative stress occurs (4,26). It is also known that some antioxidant enzymes such as Gpx-3 and Sod-1 suppress this oxidative stress (28–30).