scholarly journals Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zewen Liu ◽  
Tingyang Zhou ◽  
Alexander C. Ziegler ◽  
Peter Dimitrion ◽  
Li Zuo

Increasing numbers of individuals, particularly the elderly, suffer from neurodegenerative disorders. These diseases are normally characterized by progressive loss of neuron cells and compromised motor or cognitive function. Previous studies have proposed that the overproduction of reactive oxygen species (ROS) may have complex roles in promoting the disease development. Research has shown that neuron cells are particularly vulnerable to oxidative damage due to their high polyunsaturated fatty acid content in membranes, high oxygen consumption, and weak antioxidant defense. However, the exact molecular pathogenesis of neurodegeneration related to the disturbance of redox balance remains unclear. Novel antioxidants have shown great potential in mediating disease phenotypes and could be an area of interest for further research. In this review, we provide an updated discussion on the roles of ROS in the pathological mechanisms of Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinocerebellar ataxia, as well as a highlight on the antioxidant-based therapies for alleviating disease severity.

2021 ◽  
Vol 11 (5) ◽  
pp. 2228
Author(s):  
Daniela Galli ◽  
Cecilia Carubbi ◽  
Elena Masselli ◽  
Mauro Vaccarezza ◽  
Valentina Presta ◽  
...  

Reactive Oxygen Species (ROS) are molecules naturally produced by cells. If their levels are too high, the cellular antioxidant machinery intervenes to bring back their quantity to physiological conditions. Since aging often induces malfunctioning in this machinery, ROS are considered an effective cause of age-associated diseases. Exercise stimulates ROS production on one side, and the antioxidant systems on the other side. The effects of exercise on oxidative stress markers have been shown in blood, vascular tissue, brain, cardiac and skeletal muscle, both in young and aged people. However, the intensity and volume of exercise and the individual subject characteristics are important to envisage future strategies to adequately personalize the balance of the oxidant/antioxidant environment. Here, we reviewed the literature that deals with the effects of physical activity on redox balance in young and aged people, with insights into the molecular mechanisms involved. Although many molecular pathways are involved, we are still far from a comprehensive view of the mechanisms that stand behind the effects of physical activity during aging. Although we believe that future precision medicine will be able to transform exercise administration from wellness to targeted prevention, as yet we admit that the topic is still in its infancy.


2020 ◽  
Vol 26 (12) ◽  
pp. 1251-1262 ◽  
Author(s):  
Octavio Binvignat ◽  
Jordi Olloquequi

: The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as the injury and death of neurons due to excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. : Despite the anti-excitotoxic drug memantine has shown modest beneficial effects in some patients with dementia, to date, there is no effective treatment capable of halting or curing neurodegenerative diseases such as Alzheimer’s disease, Parkinson disease, Huntington’s disease or amyotrophic lateral sclerosis. This has led to a growing body of research focusing on understanding the mechanisms associated with the excitotoxic insult and on uncovering potential therapeutic strategies targeting these mechanisms. : In the present review, we examine the molecular mechanisms related to excitotoxic cell death. Moreover, we provide a comprehensive and updated state of the art of preclinical and clinical investigations targeting excitotoxic- related mechanisms in order to provide an effective treatment against neurodegeneration.


2021 ◽  
Vol 7 (3) ◽  
pp. eabd9036
Author(s):  
Sara Saez-Atienzar ◽  
Sara Bandres-Ciga ◽  
Rebekah G. Langston ◽  
Jonggeol J. Kim ◽  
Shing Wan Choi ◽  
...  

Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated six differentially expressed genes (ATG16L2, ACSL5, MAP1LC3A, MAPKAPK3, PLXNB2, and SCFD1) within the significant pathways as relevant to ALS. We conclude that the disparate genetic etiologies of this fatal neurological disease converge on a smaller number of final common pathways and cell types.


Diversity ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 105
Author(s):  
Amirah Yuslan ◽  
Sharifah Najuwa ◽  
Atsushi Hagiwara ◽  
Mazlan A. Ghaffar ◽  
Hidayu Suhaimi ◽  
...  

Salinity is a known factor in shaping population dynamics and community structure through direct and indirect effects on aquatic ecosystems. Salinity changes further influence food webs through competition and predation. The responses of Moina macrocopa (Cladocera) collected from Setiu Wetland lagoon (Terengganu) was evaluated through manipulative laboratory experiments to understand the ability of M. macrocopa to tolerate high salinity stress. Specifically, the fatty acid composition, growth, survival, and reproduction of this cladocerans species was examined. Sodium chloride (NaCl) as used in the treatments water with the concentration 0, 4, 6, 8, 12, and 15 salinity. Fatty acid levels were determined using Gas Chromatography and Mass Spectrophotometry (GC-MS). The results indicated that optimal conditions produced the highest fatty acid content, especially the polyunsaturated fatty acid content, such as EPA (eicosapentaenoic acid), ALA (alpha-linoleic acid), ARA (arachidonic acid), and DHA (docosahexaenoic acid). Furthermore, M. macrocopa survival was best at salinity 0, with a percentage of 98%, whereas the opposite occurred at salinity 15, with approximately 20% of viable animals surviving. Besides, M. macrocopa also showed the highest reproduction rate at salinity 0 (e.g., average initial age of reproduction, 4.33 ± 0.58 days) compared with other salinities level. Interestingly, the difference in growth at different salinities was not evident, an unusual finding when considering adverse effects such as osmoregulation pressure on the organism. Based on the results, we conclude that M. macrocopa can only tolerate salinity below salinity 8 and cannot withstand stressful environmental conditions associated with salinities above 8.


Lipid / Fett ◽  
1996 ◽  
Vol 98 (4) ◽  
pp. 141-144 ◽  
Author(s):  
W. De Greyt ◽  
M. Kellens ◽  
A. Huyghebaerts

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Arash Mollaeian ◽  
Jingjing Chen ◽  
Nina N. Chan ◽  
Gregory A. Nizialek ◽  
Christopher J. Haas

Abstract Background Adult onset Still’s disease (AOSD) is a rare inflammatory disorder that classically presents with high spiking fevers, evanescent rash, and arthritis. The diagnosis is one of exclusion and can be further complicated by atypical presentations, particularly in elderly patients in whom AOSD is very rare. Case presentation A case of AOSD in a 73-year-old woman with a non-classic presentation, leading to delayed diagnosis and management, is presented along with a review of the English literature for AOSD cases in elderly people over 70 years of age. Thirty nine case reports and series were identified and the current case was added, totaling 42 individual cases. Significant findings included a four-times higher prevalence in females, a higher prevalence of macrophage activation syndrome despite lower mortality, the presence of pruritic rash in almost one fifth of the cases, and high prevalence of delayed diagnosis. Conclusions AOSD in the elderly may vary from the classic criteria described in the medical literature and may lead to delayed diagnosis and management. Further evaluation and better characterization of AOSD in the elderly remains an area of interest.


2017 ◽  
Vol 176 (6) ◽  
pp. R283-R308 ◽  
Author(s):  
Evanthia Diamanti-Kandarakis ◽  
Maurizio Dattilo ◽  
Djuro Macut ◽  
Leonidas Duntas ◽  
Efstathios S Gonos ◽  
...  

Aging and its underlying pathophysiological background has always attracted the attention of the scientific society. Defined as the gradual, time-dependent, heterogeneous decline of physiological functions, aging is orchestrated by a plethora of molecular mechanisms, which vividly interact to alter body homeostasis. The ability of an organism to adjust to these alterations, in conjunction with the dynamic effect of various environmental stimuli across lifespan, promotes longevity, frailty or disease. Endocrine function undergoes major changes during aging, as well. Specifically, alterations in hormonal networks and concomitant hormonal deficits/excess, augmented by poor sensitivity of tissues to their action, take place. As hypothalamic–pituitary unit is the central regulator of crucial body functions, these alterations can be translated in significant clinical sequelae that can impair the quality of life and promote frailty and disease. Delineating the hormonal signaling alterations that occur across lifespan and exploring possible remedial interventions could possibly help us improve the quality of life of the elderly and promote longevity.


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