Oxidative Stress in Alzheimer’s Disease: Should We Keep Trying Antioxidant Therapies?

Abstract

The risk of chronic diseases such as Alzheimer's disease is growing as a result of the continuous increasing average life span of the world population, a syndrome characterized by the presence of intraneural neurofibrillary tangles and senile plaques composed mainly by beta-amyloid protein, changes that may cause a number of progressive disorders in the elderly, causing, in its most advanced stage, difficulty in performing normal daily activities, among other manifestations. Therefore, it is important to understand the underlying pathogenic mechanisms of this syndrome. Nevertheless, despite intensive effort to access the physiopathological pathways of the disease, it remains poorly understood. In that context, some hypotheses have arisen, including the recent oxidative stress hypothesis, theory supported by the involvement of oxidative stress in aging, and the vulnerability of neurons to oxidative attack. In the present revision, oxidative changes and redox mechanisms in Alzheimer's disease will be further stressed, as well as the grounds for antioxidant supplementation as adjuvant therapy for the disease will be addressed.

Protective effects of Sanguisorba minor and Ferulago angulata total extracts against beta-amyloid induced cytotoxicity and oxidative stress in cultured cerebellar granule neurons

“…Also, Aβ-induced increase in ROS production and decrease in GPx activity, as an antioxidant enzyme, were significantly restored by pretreatment with S. minor and F. angulata extracts which indicates that Aβ-induced oxidative stress was significantly attenuated by these extracts. Several studies have reported that Aβ peptide in aggregated form produced neurotoxicity and has a pivotal role in neural cell loss and progression of AD disease and also oxidative stress plays crucial roles in Aβ-induced toxicity (8,33,34). Medicinal plants which are rich in polyphenol compounds have strong antioxidant activity and protects neurons from oxidative insults (35).…”

“…Poly-D-lysine (PDL) was purchased from Santa Cruz Biotechnology Inc. (USA). Beta amyloid peptide (AB [25][26][27][28][29][30][31][32][33][34][35] was purchased from Enzo Life Sciences (Farmingdale, USA). All other materials were purchased from Sigma (USA).…”

Applications of the Keap1–Nrf2 system for gene and cell therapy

“…Oxidative stress is one of the main pathophysiological features in chronic neurological disorders, such as Alzheimer's disease (AD) [55][56][57][58][59] , Parkinson's disease (PD) [60][61][62] , amyotrophic lateral sclerosis (ALS) [63][64][65][66] , and epilepsy [67][68][69] . Acute CNS injuries, such as stroke, traumatic brain injury (TBI) and traumatic SCI are also characterized by excessive oxidative stress [70][71][72][73][74] .…”

“…Several pathophysiological mechanisms including excitotoxicity, mitochondrial dysfunction, metal dyshomeostasis, neuroinflammation and oxidative stress participate in AD pathology. However, in the case of AD, increased oxidative stress is not only a significant component of pathology exacerbating the neurodegenerative process [55][56][57][58][59] , but it is also believed to be one of the earliest events in the disease development that could even precede Aβ deposition [122] . Oxidative stress may stimulate Aβ production [123,124] , as well as tau hyperphosphorylation and polymerization [125,126] .…”

Involvement of neuroinflammatory mediators in the pathogenesis of neurodegeneration

“…Third, the high levels of polyunsaturated fatty acids are found in the brain cell membranes and react as substrates for lipid peroxidation www.ajpp.in (Wang et al, 2010). Fourth, there are relatively low levels of GSH in the brain, which plays a role of endogenous antioxidant in the elimination of ROS (Ferreira et al, 2015).…”