Antioxidant defense in Alzheimer's disease

However, the mechanisms that create free radicals and prompt redox uneven characters stay elusive. Mitochondrial dysfunction as well as a sporadic movement of metals forming reactive oxygen species (ROS), which exorbitant accumulation of Amyloid beta (Aβ) and tau proteins exacerbate redox imbalances. So far, no defined source of oxidative stress has been distinguished in AD. Therefore, more research on the role of oxidative stress mechanisms may prompt novel clinical intercession. The resultant oxidative pressure may amplify the generation and conglomeration of Aβ and encourage the phosphorylation and polymerization of tau, and thus designing an interminable circle that advances the inception, improvement, and movement of AD. Butterfield & Kanski, 2001), responsible for marking oxidative harm to DNA and RNA [8-hydroxydeoxyguanosine (8-OHdG) and 8-hydroxyguanosine](P. Gabbita, Lovell, & Markesbery, 1998; A Nunomura et al. and finally products of lipid peroxidation malondialdehyde (MDA), 4-hydroxynonenal, and F2-isoprostanes] are elevated in AD brains (Domenico Praticò & Sung, 2004).

OXIDATIVE STRESS AND ALZHEIMER’S DISEASE Oxidative Stress and Amyloid beta. Abnormal synthesis of Aβ occurs through sequential cleavage of amyloid precursor protein (APP) by two membrane-bound proteases β-secretase (β-site APP cleaving enzyme-BACE1), and γ-secretase [a multiprotein complex that compromise presenilin (PS), nicastrin (NCT), anterior pharynx-defective one (APH-1), and presenilin foil macromolecule a pair of (PEN-2)]. Mitochondria Dysfunction and Oxidative Stress in AD The mitochondrial anomalies were accompanied by oxidative destruction discernable by 8-hydroxyguanosine and nitrotyrosine that depicts the removal of mitochondria in the midst of AD development (Hirai et al. Compromised Oxidative Stress Defense Mechanisms in AD Brain GSH can react with free radicals either independently or in the reaction catalyzed by glutathione peroxidase (GPx) to form glutathione disulfide (GSSG) that can be converted to a diminished state by glutathione reductase.

STRATEGIES TO COMBAT OXIDATIVE STRESS Endogenous Antioxidants The endogenous non-enzymatic antioxidants in the body are glutathione, NADPH, uric acid, bilirubin, the iron-binding protein transferrin and ferritin, α-lipoic acid, melatonin, and reduced CoQ10, which take part in protecting the body from ROS and their byproducts produced amid typical cellular metabolism. GSH is one of the most critical components that plays a significant role in xenobiotic metabolism by preventing oxidative damage caused by ROS (lipid peroxides like hydroxynonenal). GSH role as an antioxidant can diminish during xenobiotic neutralization. Current evidence suggests that antioxidant therapy might offer promising therapeutic benefits for AD. Several antioxidants have been investigated to alter the pathophysiology of AD. The subsequent sections describe the conventional and novel antioxidants, which have been studied in AD. Traditional Herbal Antioxidants Bacopa Monnieri (Brahmi) is a traditional plant commonly used in Ayurvedic medicine to treat several neurological diseases.

Its main constituents incorporates the saponins and triterpenoid bacosaponins which comprises of bacopasides III to V, and bacosides A and B, and also bacosaponins A, B, and C. Several other traditional herbals exhibit antioxidant effects and are found to be of therapeutic value in AD. Coptidis Rhizoma, known as Huang Lian in China, is the dried rhizome of medicinal plants from the family Ranunculaceae. Its major alkaloids groenlandicine, berberine, and palmatine act through cholinesterase and Aβ pathways as well as inhibit ROS and RNS respectively (Jung et al. Herb milk thistle (Silybum marianum), contains silibinin (silybin), a flavonoid which has antioxidative properties. In AD mice, silibinin prevented memory impairment and oxidative damage induced by Aβ and thus may be a potential therapeutic agent for Alzheimer’s disease (P.