Evidence of oxidative damage in Alzeimer’s disease brain: Central role for amyloid β-peptide

Dept of Chemistry, Center of Membrane Sciences and Sanders-Brown Center on Aging, University of Kentucky, Lexington 40506-0055, USA.
Trends in Molecular Medicine (Impact Factor: 9.45). 01/2002; 7(12):548-54. DOI: 10.1016/S1471-4914(01)02173-6
Source: PubMed


Amyloid beta-peptide (Abeta) is heavily deposited in the brains of Alzheimer's disease (AD) patients. Free-radical oxidative stress, particularly of neuronal lipids, proteins and DNA, is extensive in those AD brain areas in which Abeta is abundant. Recent research suggests that these observations might be linked, and it is postulated that Abeta-induced oxidative stress leads to neurodegeneration in AD brain. Consonant with this postulate, Abeta leads to neuronal lipid peroxidation, protein oxidation and DNA oxidation by means that are inhibited by free-radical antioxidants. Here, we summarize current research on phospholipid peroxidation, as well as protein and DNA oxidation, in AD brain, and discuss the potential role of Abeta in this oxidative stress.

Download full-text


Available from: Alessandra Castegna, May 26, 2015
  • Source
    • "The therapeutic potential of rosemary diterpenes for AD must be seen in conjunction with the role of oxidantantioxidant mechanisms in the pathology of the disease. A number of studies have clearly outlined the direct association between ROS-mediated macromolecular cell damage and neuronal cell death in AD, particularly in brain regions where Aí µí»½ is highly prevalent[106,107]. Interestingly, neuronal cells in the brain appear to be more susceptible to ROSmediated cell damage than any other cell types for numerous reasons including high oxygen consumption[108], high level of polyunsaturated fatty acids content of cell membrane[109], association of the NMDA receptor activation with ROSinduced neuronal apoptosis[110], and poor level of antioxidant defences including the catalase, glutathione peroxidase , and vitamin E contents[111]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Rosemary ( Rosmarinus officinalis L.) is one of the most economically important species of the family Lamiaceae. Native to the Mediterranean region, the plant is now widely distributed all over the world mainly due to its culinary, medicinal, and commercial uses including in the fragrance and food industries. Among the most important group of compounds isolated from the plant are the abietane-type phenolic diterpenes that account for most of the antioxidant and many pharmacological activities of the plant. Rosemary diterpenes have also been shown in recent years to inhibit neuronal cell death induced by a variety of agents both in vitro and in vivo . The therapeutic potential of these compounds for Alzheimer’s disease (AD) is reviewed in this communication by giving special attention to the chemistry of the compounds along with the various pharmacological targets of the disease. The multifunctional nature of the compounds from the general antioxidant-mediated neuronal protection to other specific mechanisms including brain inflammation and amyloid beta (A β ) formation, polymerisation, and pathologies is discussed.
    Full-text · Article · Jan 2016 · Evidence-based Complementary and Alternative Medicine
  • Source
    • "Oxidative and nitrosative stress, the result of increased levels of reactive oxygen and nitrogen species, respectively, have been reported in AD brains before the accumulation of Aβ and phosphorylated tau (Reed et al., 2009;Smith et al., 1997). The production of reactive oxygen and nitrogen species is both exacerbated by, and can induce the formation of, Aβ and phosphorylated tau (Butterfield et al., 2001). In addition, disruptions to neuronal calcium signalling, mitochondrial dysfunction, and inflammation caused by the activation of microglia, have all been reported to contribute to AD pathogenesis (Mattson, 2002;Wang et al., 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer’s disease (AD) is a neurodegenerative disorder involving the loss of neurons in the brain which leads to progressive memory loss and behavioral changes. To date, there are only limited medications for AD and no known cure. Nitric oxide (NO) has long been considered part of the neurotoxic insult caused by neuroinflammation in the Alzheimer’s brain. However, focusing on early developments, prior to the appearance of cognitive symptoms, is changing that perception. This has highlighted a compensatory, neuroprotective role for NO that protects synapses by increasing neuronal excitability. A potential mechanism for augmentation of excitability by NO is via modulation of voltage-gated potassium channel activity (Kv7 and Kv2). Identification of the ionic mechanisms and signaling pathways that mediate this protection is an important next step for the field. Harnessing the protective role of NO and related signaling pathways could provide a therapeutic avenue that prevents synapse loss early in disease.
    Full-text · Article · Jan 2016 · Oxidative medicine and cellular longevity
  • Source
    • "The most representative are abnormal protein aggregation (Ross & Poirier, 2005), proteasomal (Halliwell, 2006) or autophagic dysfunction (McCray & Taylor, 2008), inflammation (Zipp & Aktas, 2006), neuronal apoptosis (Okouchi et al., 2007), oxidative stress (Andersen, 2004), mitochondrial dysfunction (Lin & Beal, 2006), and abnormal interactions between neurons and glia that accentuate the inflammatory status (Carnevale et al., 2007). Among them, mitochondrial dysfunction, reactive gliosis and oxidative damage to lipids, proteins and DNA, have been widely described in AD (Butterfield et al., 2001; Shaftel et al., 2008), PD (Alam et al., 1997; Clements et al., 2006), HD (Browne & Beal, 2006), ALS (Goodall & Morrison, 2006), and ischemic stroke (Olmez & Ozyurt, 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neurodegenerative diseases (NDDs) are predicted to be the biggest health concern in this century and the second leading cause of death by 2050. The main risk factor of these diseases is aging, and as the aging population in Western societies is increasing, the prevalence of these diseases is augmenting exponentially. Despite the great efforts to find a cure, current treatments remain ineffective or have low efficacy. Increasing lines of evidence point to exacerbated oxidative stress, mitochondrial dysfunction and chronic neuroinflammation as common pathological mechanisms underlying neurodegeneration. We will address the role of the nuclear factor E2-related factor 2 (Nrf2) as a potential target for the treatment of NDDs. The Nrf2-ARE pathway is an intrinsic mechanism of defence against oxidative stress. Nrf2 is a transcription factor that induces the expression of a great number of cytoprotective and detoxificant genes. There are many evidences that highlight the protective role of the Nrf2-ARE pathway in neurodegenerative conditions, as it reduces oxidative stress and neuroinflammation. Therefore, the Nrf2 pathway is being increasingly considered a therapeutic target for NDDs. Herein we will review the deregulation of the Nrf2 pathway in different NDDs and the recent studies with Nrf2 inducers as "proof-of-concept" for the treatment of those devastating pathologies.
    Full-text · Article · Nov 2015 · Pharmacology [?] Therapeutics
Show more