Page 11 - BH-2-2

Brain & Heart Oxidative stress and neurological disorders

increased production of free radicals, which are responsible High glucose levels elevate the production of ROS,
for age-associated functional damage to macromolecules. which transforms mitochondrial enzymes, consumption,
39
This heightened production of ROS during aging induces and deposition of nutrients, ultimately resulting in
various physiological changes, such as the inhibition metabolic disorders. In obese individuals, mitochondrial
48
of cell proliferation and the production of interleukins, dysfunctioning leads to decreased fatty acid oxidation and
chemokines, and other proinflammatory components, energy generation. ROS alter the metabolism of lipids and
ultimately leading to cell senescence. Cellular senescence fats and elevates the rate of apoptosis. 49
40
contributes to the onset of several acute and chronic
disorders, as aging disrupts cellular homeostasis, 5.3. Inflammation
particularly through oxidative damage. Oxidative stress- Inflammation represents a biological response to external
induced aging triggers mitochondrial dysfunction, further stimuli, constituting a complex immune protective
exacerbating cellular aging. As a result, the lifespan of cells mechanism of the body against external injury, allergy, or
is reduced due to the functional inefficiency of enzymes, chemical irritants. Chronic inflammation can precipitate
50
proteins, and other biomolecules. In addition, oxidative diseases related to a hyperresponsive immune system,
9
stress accelerates peroxidative damage to membrane such as rheumatoid arthritis, chronic asthma, and other
lipids, degrades membrane proteins, and reduces the neurological disorders. Tissues injured by trauma undergo
concentration of fatty lipids. ROS also play a role in cellular death or injury, releasing ROS, superoxide
51
premature aging by causing errors in DNA replication, anion, hydrogen peroxide, nitric oxide, and cytokines.
accumulation of DNA modifications, insufficient organelle Chronic inflammation is a major contributor to free
turnover, and impaired proteosis. 41 radical production, thereby playing a pivotal role in the
onset of numerous diseases. In CNS, inflammatory lesions
5.2. Obesity produced as an immune response consist of CD4+ and
Obesity, characterized by excessive body fat, exerts CD8+ T-cells. The higher accumulation of immune cells
52
multifactorial effects on health, increasing the risk of various correlates with an elevated expression of inflammatory
health problems. It typically arises from a surplus intake of cytokines. NRLP3 serves as an intracellular sensor
calories not offset by physical exercise and daily activities. detecting environmental stimuli and endogenous danger
42
Obesity has been associated with systemic oxidative stress, signals. Chronic inflammation activates NRLP3, leading
which stems from increased production of adipokines to the formation of inflammasomes, which, in turn,
and the development of metabolic syndrome. Oxbiosis- induces mitochondrial dysfunction, resulting in increased
43
induced oxidative stress is attributed to increased adipocyte production of mitochondrial ROS. The NF-κB pathway is
numbers that lead to elevated levels of proinflammatory intricately interconnected with various cellular pathways
cytokines such as interleukin-6 and indicative of chronic and inflammation. This transcription factor plays an
5
inflammation within the body. Moreover, the increased important role in maintaining cellular homeostasis and
44
mechanical load and myocardial demand associated with is markedly upregulated during aging, contributing to
obesity escalate oxygen consumption, resulting in the chronic inflammation. Activation of the NF-κB pathway
overproduction of free radicals. Jia et al. suggest that if amplifies inflammatory responses through positive
45
obesity persists for a prolonged duration, antioxidants such feedback, leading to an increase in ROS/RNS within cells,
as catalase and SOD also become depleted. As adipocytes thereby fostering stressful conditions within the cellular
increase, cellular metabolism is affected, leading to an environment. 53
overproduction of ROS. Weight loss, along with antioxidant
supplements such as Vitamin E, can help reduce the 5.4. Mitochondrial dysfunction
pathologies related to oxidative stress. Even at the hepatic After the nucleus, only the mitochondria is the cell organelle
45
level, obesity induces lipid peroxidation, oxidative stress, having its own DNA. Due to the activity of electron
and autophagy. ROS are involved in the signal transduction chain transport, ROS are a major byproduct within the
46
and differentiation of adipocytes from stem cells. However, mitochondria. Oxidative stress-related disarrangements
54
complete information about this process still needs to be within the mitochondria and proinflammatory signaling
elucidated, as it involves many transcription factors, cell are indicators of neurodegeneration. Mitochondria form
cycle proteins, small molecules, and hormones. Elevated an interconnected network with other organelles such as
47
ROS levels may result in modified differentiation of lysosomes, endoplasmic reticulum, actin cytoskeleton,
adipocytes and their function, and also alter the browning and the Golgi apparatus. Neuroinflammation is linked to
process in obesity. Accumulation of fatty acids and lipids is many neurological disorders, in which mitochondrial-
4
accompanied by alterations in insulin signaling pathways. derived vesicles are a common factor in disease progression.

Volume 2 Issue 2 (2024) 5 doi: 10.36922/bh.2704