Cellular stress response, sirtuins and UCP proteins in Alzheimer disease: role of vitagenes

Abstract

Alzheimer’s Disease (AD) is a neurodegenerative disorder affecting up to one third of individuals reaching the age of 80. Different integrated responses exist in the brain to detect oxidative stress which is controlled by several genes termed Vitagenes. Vitagenes encode for cytoprotective heat shock proteins (Hsp), as well as thioredoxin, sirtuins and uncouple proteins (UCPs). In the present study we evaluate stress response mechanisms in plasma and lymphocytes of AD patients, as compared to controls, in order to provide evidence of an imbalance of oxidant/antioxidant mechanisms and oxidative damage in AD patients and the possible protective role of vitagenes.We found that the levels of Sirt-1 and Sirt-2 in AD lymphocytes were significantly higher than in control subjects. Interestingly, analysis of plasma showed in AD patients increased expression of Trx, a finding associated with reduced expression of UCP1, as compared to control group.This finding can open up new neuroprotective strategies, as molecules inducing this defense mechanisms can represent a therapeutic target to minimize the deleterious consequences associated to oxidative stress, such as in brain aging and neurodegenerative disorders.

Methionine Sulfoxide Reductase A Negatively Controls Microglia-Mediated Neuroinflammation via Inhibiting ROS/MAPKs/NF-κB Signaling Pathways Through a Catalytic Antioxidant Function

“…However, there is much less evidence related to their participation in the function of microglia. It has been demonstrated that both SOD-1 and peroxiredoxin I inhibit microglial activation and exert significant anti-inflammatory effects (6,10,24,29). Here, we found that SOD-1 rapidly transforms superoxide into hydrogen peroxide, which also acts as a second messenger to mediate signal transduction and regulate microglial status (15,21,58).…”

“…To maintain redox homeostasis, vitagenes network, an emerging concept that includes a group of genes involved in preserving cellular homeostasis during stressful conditions, operates actively to preserve neuron survival and serves as an integrated mechanism (6,7,10,60). Vitagenes encode for cytoprotective proteins such as heat shock proteins, the thioredoxin, and the sirtuin protein systems and their expression can be activated by oxidative stress or dietary antioxidants, such as polyphenols.…”

Novel Blood Biomarkers Are Associated with White Matter Lesions in Fragile X- Associated Tremor/Ataxia Syndrome

“…On the other hand, it is likely that the observed mitochondrial hyperactivity represents an activation of blood lymphocytes in their reported neuroprotective and sometimes neuroantagonistic roles. Indirect evidence for the postulated role of blood lymphocytes in mediating increased oxidative stress to neurones leading to cell death, or in alleviating inflammatory aspects of neurodegenerative processes, has been presented in rare experimental or human studies of Alzheimer's disease [17,18,19]. Moreover, important and relevant findings on lymphocyte recruitment, activation, and infiltration in the CNS under pathological situations, including Parkinson's disease and ALS, have recently been reviewed [20].…”

Flavanonol Taxifolin Attenuates Proteasome Inhibition-Induced Apoptosis in Differentiated PC12 Cells by Suppressing Cell Death Process

“…The vitagene system as one of the main intracellular redox systems has been suggested to be involved in neuroprotection [41]. Vitagenes encode for cytoprotective heat shock protein Hsp70, the thioredoxin and the sirtuin protein systems [42,43]. Dietary antioxidants, such as polyphenols and L-carnitine/ acetyl-L-carnitine, have been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes [42,44].…”

“…The overload of toxic products derived from the free radical oxidation of protein, polyunsaturated fatty acids and cholesterol contribute to the disruption of the cellular redox homeostasis, which may be implicated in the pathogenesis in neurodegenerative disorders [40][41][42][43]. The vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions [40].…”