Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain

Mecocci, Patrizia; Beal, M. Flint; Cecchetti, Roberta; Polidori, Maria Cristina; Cherubini, Antonio; Chionne, Fausto; Avellini, Luca; Romano, Giustina; Senin, Umberto

doi:10.1007/bf02815160

Cited by 202 publications

(102 citation statements)

References 44 publications

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“…Mecocci et al found a small but significant increase in oxidative damage to nDNA in patient brain samples and a highly significant threefold increase in oxidative damage to mtDNA in AD compared with agematched controls [11] . Later, the same authors found a significant reduction of mitochondrial membrane fluidity in AD [12] . 4.…”

Section: Sugars: An Increased Glycation and Glycoxidationmentioning

confidence: 82%

Is antioxidant therapy effective to treat alzheimer's disease?

Lloret

Giraldo

Viña

2011

Free Radicals and Antioxidants

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Section: Sugars: An Increased Glycation and Glycoxidationmentioning

confidence: 82%

Is antioxidant therapy effective to treat alzheimer's disease?

Lloret

Giraldo

Viña

2011

Free Radicals and Antioxidants

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“…Incomplete reduction of oxygen increases ROS, which are known to impair the structural integrity of the inner mitochondrial membrane result in a reduction of the efficiency of the electron transport chain. 38 Furthermore, increased ROS oxidizes both proteins and DNA thus promoting apoptosis. 39 In addition to the potential central nervous system toxicity from increased ROS generation, increasing oxygenation could also lead to cerebral vasoconstriction, resulting in reduced perfusion in the brain.…”

Section: Mitochondrial Dysfunction and Normobaric Oxygenmentioning

confidence: 99%

Normobaric Oxygen Worsens Outcome after a Moderate Traumatic Brain Injury

Watts

Long

Manga

et al. 2015

J Cereb Blood Flow Metab

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Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO (n = 8) or normal air (n = 8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI.

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“…For example, recent studies have demonstrated a decline in polyunsaturated fatty acids (PUFA) [19,20], increased levels of lipid peroxidation markers [19,21,22], as well as protein oxidation [23,24], DNA oxidation [25][26][27] and RNA oxidation [28][29][30][31] during AD. Additionally, the presence of oxidative stress markers such as advanced glycation end products (AGE), glycoxidative end products, e.g., N ε -carboxymethyllysine and lipid peroxidation adducts are detected in both NFT and senile plaques in AD [21][22][23][24][32][33][34][35] Interestingly, our recent finding demonstrated ultrastructural features of vascular lesions and mitochondria in brain vascular wall cells from human AD brain biopsy are also suggestive of oxidative damage [45,46].…”

Section: Vascular Oxidative Stress In Alzheimer Diseasementioning

confidence: 99%

Vascular oxidative stress in Alzheimer disease

Zhu

Smith

Honda

et al. 2007

Journal of the Neurological Sciences

160

156

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Alzheimer disease and cerebrovascular dementia are two common causes of dementia and, by present diagnostic criteria, are mutually exclusive using vascular pathology as an arbitrary demarcation in differential diagnosis. However, evidence from epidemiological, neuropathological, clinical, pharmacological, and functional studies suggest considerable overlap in risk factors and pathological changes suggesting shared common pathogenic mechanisms between these two diseases such that vascular factors play a vital role in the pathogenesis of Alzheimer disease. A high energy demand and lack of an endogenous fuel reserve make the brain highly dependent upon a continuous blood supply where disruption of cerebral blood vessels and blood flow can have serious consequences on neural activities. Indeed, many studies implicate metabolic defects in Alzheimer disease, such a reduced brain metabolism is one of the best documented abnormalities in the disease. Notably, since endothelial reactive oxygen species such as nitric oxide act as vasodilators at low concentrations, increased production coupled with elevated reactive oxygen species scavenging of nitric oxide, can lead to reduced bioavailability of nitric oxide and increased oxidative stress that damage sensitive vascular cells. In this respect, we and others have demonstrated that oxidative stress is one of the earliest pathological changes in the brain of Alzheimer disease patients and plays a critical role in the vascular abnormalities underlying metabolic defects in Alzheimer disease. Here, we discuss vascular factors in relation to Alzheimer disease and review hypoperfusion as a potential cause by triggering mitochondrial dysfunction and increased oxidative stress initiating the pathogenic process. KeywordsAlzheimer disease; hypoperfusion; mitochondria; nitric oxide; nitric oxide synthase; oxidative stress; vascular abnormalitiesCorrespondence to: George Perry, Ph.D., College of Sciences, University of Texas at San Antonio, 6900 North Loop 1604 West, San Antonio, Texas 78249-0661 USA, , george.perry@utsa.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. . Therefore, perivascular Aβ deposits may be a risk factor for reduced regional CBF [7]. Ultrastructural studies on blood vessels associated with Aβ deposits have shown their intermittent association with membrane abnormalities of smooth muscle cells [5]. Indeed, in AD cases with a clinical history of cerebral bleeding, the muscle layer is sometimes completely replaced by Aβ deposits, suggesting that the vascular system may be an initiator for the development of diseas...

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Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain

Cited by 202 publications

References 44 publications

Is antioxidant therapy effective to treat alzheimer's disease?

Is antioxidant therapy effective to treat alzheimer's disease?

Normobaric Oxygen Worsens Outcome after a Moderate Traumatic Brain Injury

Vascular oxidative stress in Alzheimer disease

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