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Natural Product Compounds from Plants in Neurodegenerative Diseases
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Priya Darshani, Md TanjimAlam, Prem P. Tripathi, V.S. Pragadheesh
ALS is an irreversible and progressive neurodegenerative disease associated with selective motor neuron death in the spinal cord, brain stem and motor cortex. The progressive loss of motor neurons leads to muscle weakening, atrophy and dysfunction, resulting in final respiratory failure. ALS affects the nerve cells in the CNS and PNS (peripheral nervous system), causing loss of muscle control. Protein aggregates of TAR DNA-binding protein 43 (TDP-43) have been reported in patients with ALS (Van Es et al., 2017). Mutation of the superoxide dismutase-1 (SOD1) gene has been attributed to the development of this disease (Ciesler and Youssef, 2013).
Vitamin C in Neurological Function and Neurodegenerative Disease
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Shilpy Dixit, David C. Consoli, Krista C. Paffenroth, Jordyn M. Wilcox, Fiona E. Harrison
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder in which the neurons of the motor cortex, brainstem, and spinal cord progressively degenerate, leading to a debilitating loss of motor function. It is not yet known why motor neurons are specifically targeted, but genetic mutations appear to contribute significantly to the nearly identical manifestation of both the familial and sporadic forms of the disease. As with other neurodegenerative diseases, protein inclusions visible within the cytoplasm of motor neurons are pathologic hallmarks of ALS. These aggregates are composed of highly ubiquitinated protein products made unstable by gene mutations, such as cytoplasmic Cu/Zn superoxide dismutase 1 (Cu/Zn-SOD1) [252]. In fact, the missense and truncation mutations in SOD1 were the first genetic mutations to be associated with ALS due to the abundance of both mutant and wild-type SOD1 found in the aggregates. The discovery of this gene association with ALS along with other genes involved in mitochondrial function suggest that oxidative stress plays a significant role in the pathogenesis of the disease [252,253]. Cu/Zn-SOD1 specifically reduces cytoplasmic superoxide anions to hydrogen peroxide molecules, which are then neutralized by other antioxidant enzymes. At higher concentrations, vitamin C also effectively scavenges superoxide [254], thus providing a secondary antioxidant defense in maintaining redox homeostasis.
Chronic Hyperglycemia Impairs Vision, Hearing, and Sensory Function
Published in Robert Fried, Richard M. Carlton, Type 2 Diabetes, 2018
Robert Fried, Richard M. Carlton
The lenses of diabetic individuals have impaired antioxidant capacity, increasing their susceptibility to oxidative stress. This is exacerbated by inactivation of lens antioxidant enzymes like copper-zinc superoxide dismutase 1 (SOD1), the most dominant superoxide dismutase enzyme in the lens (Ookawara, Kawamura, Kitagawa et al. 1992; Behndig, Karlsson, Johansson et al. 2001). The enzyme SOD1 degrades superoxide radicals (O2−) into hydrogen peroxide (H2O2) and oxygen. The importance of SOD1 in protection against cataract development in the presence of diabetes is the reason for its being featured in a later chapter.
Frequency of C9orf72 and SOD1 mutations in 302 sporadic ALS patients from three German ALS centers
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2023
Rüstem Yilmaz, Torsten Grehl, Lukas Eckrich, Ines Marschalkowski, Kanchi Weishaupt, Ivan Valkadinov, Melita Simic, David Brenner, Peter M. Andersen, Joachim Wolf, Jochen H. Weishaupt
That 8.9% of patients have C9orf72 HRE is surprisingly high when compared to the 5% of European SALS patients detected by Zou et al. (5), while three out of 302 patients with a SOD1 variant was close to the expected range of an estimated 1.2–1.5% global frequency of SALS (22). The comparably high number of C9orf72 mutant patients in SALS cohorts can at least partially be attributed to the incomplete penetrance of C9orf72 that is age-dependent (23). Other relevant factors are most likely partially missing family history, missed diagnosis, pleiotropy, or demise of family members due to other reasons before the onset of ALS. Moreover, C9orf72 HRE can manifest as both ALS, frontotemporal dementia or movement disorder, thereby obscuring the familial aspect. In this study, we excluded patients who had a history of neurodegenerative disorders in the family such as dementia. It is also important to emphasize that both SOD1 mutations that we detected in our cohort belong to the rare instances of SOD1 variants that can cause also recessively inherited ALS, and may therefore be enriched in ALS cases categorized as sporadic.
Neuroprotective benefits of grape seed and skin extract in a mouse model of Parkinson’s disease
Published in Nutritional Neuroscience, 2021
Sarah Ben Youssef, Guillaume Brisson, Hélène Doucet-Beaupré, Anne-Marie Castonguay, Charles Gora, Mohamed Amri, Martin Lévesque
Our data also show that SOD1 levels in the midbrain decrease upon 6-OHDA insult, which is in agreement with previous reports [18,19,56]. A decrease in SOD1 has been associated with some deleterious effects due to the accumulation of ROS such as superoxide radicals and hydrogen peroxide [57], both of which damage the cell membrane and other biological structures [58]. Moreover, SOD1 protects tissues against oxygen free radicals by catalyzing the removal of superoxide radicals, converting them into hydrogen peroxide and oxygen. Safwen et al. [14] revealed that GSSE treatment in ischemic rats regulates the expression of SOD2 isoforms. In addition, Balu et al. [59] demonstrated that declining SOD activity in the aged brain was returned to near-normal levels upon grape seed extract administration. In our in vivo study, SOD1 levels were found to be slightly but significantly reduced in the mice treated with 6-OHDA, while GSSE treatment helped to restore SOD1 levels. The beneficial impact of GSSE on SOD1 levels in the midbrain may partially explain the positive impact of GSSE on SNpc neuron survival observed in our in vivo model. However, the effect of GSSE, rather than bring due to the specific effect of a single compound, is likely more complex due to the putative synergism between its different polyphenols, such as catechins, quercetins, epicatechins, procyanidins, gallic acid [6].
Facial onset amyotrophic lateral sclerosis with K3E variant in the Cu/Zn superoxide dismutase gene
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2021
Kazumoto Shibuya, Setsu Sawai, Atsuhiko Sugiyama, Mizuho Koide, Ayumi Nishiyama, Masashi Aoki, Satoshi Kuwabara
Facial onset ALS has rarely been described. Two case reports described two familial ALS patients with C6G variant in SOD1 gene, who had facial onset, experienced rapid progression of weakness and died after 2–3 months after onset, due to respiratory failure (7,8). Additionally, several studies disclosed patients with facial onset sensory and motor neuronopathy (FOSMN) syndrome as a rare type motor neuron diseases (9). Moreover, a case with heterozygous D90A variant in SOD1 gene has been reported as presenting FOSMN syndrome manifestations (10). Characteristics of FOSMN syndrome are entirely distinct from those of the present case, because FOSMN is characterized by initial development of sensory involvement in the trigeminal nerve territory, and subsequent slowly progressive bulbar and upper limb amyotrophy. However, a previous animal model study, utilizing mice with G93A variant in SOD1 gene, revealed decreased motor neuron population in the facial nucleus as well as the hypoglossal nucleus. As such, several ALS patients with variants in SOD1 gene may experience a facial onset manifestation. Nevertheless, it should be stressed that ALS with variants in SOD1 almost starts in the lower limb region. Moreover, other family members of the present case experienced limb onset.