scholarly journals Multiplexed Proteomic Analysis of Oxidation and Concentrations of Cerebrospinal Fluid Proteins in Alzheimer Disease

2007 ◽  
Vol 53 (4) ◽  
pp. 657-665 ◽  
Author(s):  
Minna A Korolainen ◽  
Tuula A Nyman ◽  
Paula Nyyssönen ◽  
E Samuel Hartikainen ◽  
Tuula Pirttilä
Keyword(s):  
Oxidative Stress ◽  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Oxidative Modification ◽  
Cerebrospinal Fluid Proteins ◽  
Age Related ◽  
Aging Women ◽  
Specific Proteins ◽  
Brain Specific Proteins

Abstract Background: Carbonylation is an irreversible oxidative modification of proteins that has been linked to various conditions of oxidative stress, aging, physiological disorders, and disease. Increased oxidative stress is thus also considered to play a role in the pathogenesis of age-related neurodegenerative disorders such as Alzheimer disease (AD). In addition, it has recently become evident that the response mechanisms to increased oxidative stress may depend on sex. Several oxidized carbonylated proteins have been identified in plasma and brain of AD patients by use of 2-dimensional oxyblotting. Methods: In this pilot study, we estimated the concentrations and carbonylation of the most abundant cerebrospinal fluid proteins in aging women and men, both AD patients suffering from mild dementia and individuals exhibiting no cognitive decline. Oxidized carbonylated proteins were analyzed with 2-dimensional multiplexed oxyblotting, mass spectrometry, and database searches. Results: Signals for β-trace, λ chain, and transthyretins were decreased in probable AD patients compared with controls. The only identified protein exhibiting an increased degree of carbonylation in AD patients was λ chain. The concentrations of proteins did not generally differ between men and women; however, vitamin D–binding protein, apolipoprotein A-I, and α-1-antitrypsin exhibited higher extents of carbonylation in men. Conclusions: None of the brain-specific proteins exhibited carbonylation changes in probable AD patients compared with age-matched neurological controls showing no cognitive decline. The carbonylation status of proteins differed between women and men. Two-dimensional multiplexed oxyblotting is applicable to study both the concentrations and carbonylation of cerebrospinal fluid proteins.

scholarly journals It Is All about (U)biquitin: Role of Altered Ubiquitin-Proteasome System and UCHL1 in Alzheimer Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Antonella Tramutola ◽  
Fabio Di Domenico ◽  
Eugenio Barone ◽  
Marzia Perluigi ◽  
D. Allan Butterfield
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Ubiquitin Proteasome System ◽  
Oxidative Modification ◽  
Age Related ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
And Function ◽  
Cellular Components

Free radical-mediated damage to macromolecules and the resulting oxidative modification of different cellular components are a common feature of aging, and this process becomes much more pronounced in age-associated pathologies, including Alzheimer disease (AD). In particular, proteins are particularly sensitive to oxidative stress-induced damage and these irreversible modifications lead to the alteration of protein structure and function. In order to maintain cell homeostasis, these oxidized/damaged proteins have to be removed in order to prevent their toxic accumulation. It is generally accepted that the age-related accumulation of “aberrant” proteins results from both the increased occurrence of damage and the decreased efficiency of degradative systems. One of the most important cellular proteolytic systems responsible for the removal of oxidized proteins in the cytosol and in the nucleus is the proteasomal system. Several studies have demonstrated the impairment of the proteasome in AD thus suggesting a direct link between accumulation of oxidized/misfolded proteins and reduction of this clearance system. In this review we discuss the impairment of the proteasome system as a consequence of oxidative stress and how this contributes to AD neuropathology. Further, we focus the attention on the oxidative modifications of a key component of the ubiquitin-proteasome pathway, UCHL1, which lead to the impairment of its activity.

scholarly journals Neurogranin as Cerebrospinal Fluid Biomarker for Alzheimer Disease: An Assay Comparison Study

2018 ◽  
Vol 64 (6) ◽  
pp. 927-937 ◽  
Author(s):  
Eline A J Willemse ◽  
Ann De Vos ◽  
Elizabeth M Herries ◽  
Ulf Andreasson ◽  
Sebastiaan Engelborghs ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Clinical Performance ◽  
Lewy Bodies ◽  
Analysis Of Covariance ◽  
Group Differences ◽  
Subjective Cognitive Decline ◽  
Terminal Part ◽  
Washington University

Abstract BACKGROUND Neurogranin in cerebrospinal fluid (CSF) correlates with cognitive decline and is a potential novel biomarker for Alzheimer disease (AD) dementia. We investigated the analytical and diagnostic performance of 3 commonly used neurogranin assays in the same cohort of patients to improve the interpretability of CSF neurogranin test results. METHODS The neurogranin Erenna® assay from Washington University, St. Louis, MO (WashU); ELISA from ADx Neurosciences; and ELISA from Gothenburg University, Mölndal, Sweden (UGot), were compared using silver staining and Western blot after gel electrophoresis. Clinical performance of the 3 assays was compared in samples from individuals diagnosed with subjective cognitive decline (n = 22), and in patients with AD (n = 22), frontotemporal dementia (n = 22), dementia with Lewy bodies (n = 22), or vascular dementia (n = 20), adjusted for sex and age. RESULTS The assays detected different epitopes of neurogranin: the WashU assay detected the N-terminal part of neurogranin (S10-D23) and a C-terminal part (G49-G60), the ADx assay detected C-terminal neurogranin truncated at P75, and the UGot assay detected the C-terminal neurogranin with intact ending (D78). Spearman ρ was 0.95 between ADx and WashU, 0.87 between UGot and WashU, and 0.81 between UGot and ADx. ANCOVA (analysis of covariance) showed group differences for ranked neurogranin concentrations in each assay (all P < 0.05), with specific increases in AD. CONCLUSIONS Although the 3 assays target different epitopes on neurogranin and have different calibrators, the high correlations and the similar group differences suggest that the different forms of neurogranin in CSF carry similar diagnostic information, at least in the context of neurodegenerative diseases.

scholarly journals Brain Ageing, Cognition and Diet: A Review of the Emerging Roles of Food-Based Nootropics in Mitigating Age-related Memory Decline

2019 ◽  
Vol 12 (1) ◽  
pp. 2-14 ◽  
Author(s):  
Adejoke Yetunde Onaolapo ◽  
Adebimpe Yemisi Obelawo ◽  
Olakunle James Onaolapo
Keyword(s):  
Oxidative Stress ◽  
Cognitive Decline ◽  
Antioxidant Defense System ◽  
Food Ingredients ◽  
Memory Decline ◽  
Age Related ◽  
Brain Ageing ◽  
Nootropic Agents ◽  
Age Related Cognitive Decline ◽  
The Impact

Background: Age-related cognitive decline has been suggested to result from an increase in the brain neuron loss, which is attributable to continued derangement of the brain’s oxidant/ antioxidant balance. Increased oxidative stress and a concomitant decrease in the brain’s antioxidant defense system have been associated with functional senescence and organismal ageing. However, nature has configured certain foods to be rich sources of nootropic agents, with research showing that increased consumption of such foods or food ingredients may be protective against ageing-related memory decline. This knowledge is becoming increasingly valuable in an era when the boundary that separates food from medicine is becoming blurred. In this review, we examine extant literature dealing with the impact of ageing on brain structure and function, with an emphasis on the roles of oxidative stress. Secondly, we review the benefits of food-based antioxidants with nootropic effects and/or food-based nootropic agents in mitigating memory decline; with a view to improving our understanding of likely mechanisms. We also highlight some of the limitations to the use of food-based nootropics and suggest ways in which they can be better employed in the clinical management of age-related cognitive decline. Conclusion: While it is known that the human brain endures diverse insults in the process of ageing, food-based nootropics are likely to go a long way in mitigating the impacts of these insults. Further research is needed before we reach a point where food-based nootropics are routinely prescribed.

scholarly journals Oxidative stress-induced mitochondrial failure and vasoactive substances as key initiators of pathology favor the reclassification of Alzheimer Disease as a vasocognopathy

Nova ◽  
2008 ◽  
Vol 6 (10) ◽  
pp. 170
Author(s):  
Gjumrakch Aliev ◽  
Joséph Charles Lamanna ◽  
Ludis Morales Álvarez ◽  
Mark Eric Obrenovich ◽  
Gerardo Jesús Pacheco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Pyramidal Neurons ◽  
Cell Damage ◽  
Cell Types ◽  
Vascular Wall ◽  
Chronic Injury ◽  
Mtdna Deletions ◽  
Age Related ◽  
Brain Parenchymal

Alzheimer disease and cerebrovascular accident are two leading causes of age-related dementia. Increasing evidence supports the idea that chronic hypoperfusion is primarily responsible for the pathogenesis that underlies both disease processes. Hypoperfusion is associated with oxidative imbalance, largely due to reactive oxygen species, which is associated with other age-related degenerative disorders. Recent evidence indicates that a chronic injury stimulus induces the hypoperfusion seen in the microcirculation of vulnerable regions of the brain. This leads to energy failure, manifested by damaged mitochondrial ultrastructure. Mitochondrial derangements lead to the formation of a large number of electron-dense, ¿hypoxic¿ mitochondria and cause the overproduction of mitochondrial DNA (mtDNA) deletions, which is most likely due to double stranded breaks. Additionally, these mitochondrial abnormalities coexist with increased redox metal activity, lipid peroxidation, and RNA oxidation, all of which are well established features of Alzheimer disease pathology, prior to the appearance of amyloid b deposition. Alzheimer disease, oxidative stress occurs within various cellular compartments and within certain cell types more than others, namely the vascular endothelium, which is associated with atherosclerotic damage, as well as in pyramidal neurons and glia. Interestingly, these vulnerable cells show mtDNA deletions and oxidative stress markers only in the regions that are closely associated with damaged vessels. This evidence strongly suggests that chronic hypoperfusion induces the accumulation of the oxidative stress products. Furthermore, brain vascular wall lesions linearly correlate with the degree of neuronal and glial cell damage. We, therefore, conclude that chronic hypoperfusion is a key initiator of oxidative stress in various brain parenchymal cells, and the mitochondria appear to be primary targets for brain damage in Alzheimer disease. In this manuscript, we outline a role for the continuous accumulation of oxidative stress products, such as an abundance of nitric oxide products (via the overexpression of inducible and/or neuronal NO synthase (iNOS and nNOS respectively) and peroxynitrite accumulation, as secondary but accelerating factors compromising the blood brain barrier (BBB). If this turns out to be the case, pharmacological interventions that target chronic hypoperfusion might ameliorate the key features of dementing neurodegeneration.

scholarly journals Increased Levels of Brain Specific Proteins in the Cerebrospinal Fluid after Full Term Asphyxia 1854

1998 ◽  
Vol 43 ◽  
pp. 316-316
Author(s):  
M Blennow ◽  
K Sävman ◽  
P Ilves ◽  
M Thoresen ◽  
H Hagberg ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Full Term ◽  
Specific Proteins ◽  
Brain Specific Proteins

scholarly journals Citrulline prevents age-related LTP decline in old rats

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Antonin Ginguay ◽  
Anne Regazzetti ◽  
Olivier Laprevote ◽  
Christophe Moinard ◽  
Jean-Pascal De Bandt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Decline ◽  
Ex Vivo ◽  
Harmful Effect ◽  
Antioxidant Properties ◽  
Long Term Potentiation ◽  
Public Health Issue ◽  
Ageing Population ◽  
Age Related

AbstractThe prevalence of cognitive decline is increasing as the ageing population is considerably growing. Restricting this age-associated process has become a challenging public health issue. The age-related increase in oxidative stress plays a major role in cognitive decline, because of its harmful effect on functional plasticity of the brain, such as long-term potentiation (LTP). Here, we show that citrulline (Cit) has powerful antioxidant properties that can limit ex vivo oxidative stress-induced LTP impairment in the hippocampus. We also illustrate that a three-month Cit supplementation has a protective effect on LTP in aged rats in vivo. The identification of a Cit oxidation byproduct in vitro suggests that the antioxidant properties of Cit could result from its own oxidation. Cit supplementation may be a promising preventive nutritional approach to limit age-related cognitive decline.

scholarly journals Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease

2008 ◽  
Vol 8 (3) ◽  
pp. 451-466 ◽  
Author(s):  
Qiaojun Fang ◽  
Andrew Strand ◽  
Wendy Law ◽  
Vitor M. Faca ◽  
Matthew P. Fitzgibbon ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Huntington Disease ◽  
Specific Proteins ◽  
Brain Specific Proteins

Cerebrospinal fluid levels of brain specific proteins in optic neuritis

2004 ◽  
Vol 10 (3) ◽  
pp. 261-265 ◽  
Author(s):  
E T Lim ◽  
D Grant ◽  
M Pashenkov ◽  
G Keir ◽  
E J Thompson ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
High Risk ◽  
Optic Neuritis ◽  
Neurological Diseases ◽  
White Matter Lesions ◽  
Risk Of Progression ◽  
Specific Proteins ◽  
Brain Specific Proteins ◽  
Magnetic Resonance Imaging Mri ◽  
Oligoclonal Igg

This study evaluates levels of cerebrospinal fluid (C SF) brain-specific proteins (BSP) in subjects with optic neuritis (O N) who are at high risk of progression to multiple sclerosis (MS). Forty-one subjects had acute O N and 17 subjects with other neurological diseases (OND) served as controls. Twenty-o ne subjects with O N had white matter lesions on magnetic resonance imaging (MRI) and intrathecal synthesis of oligoclonal IgG bands (OB) consistent with being at high risk of progression to MS; eight of whom later were diagnosed with clinically definite MS (C DMS). Levels of S100B, ferritin and two neurofilament heavy chain phosphoforms (NfHSMI34 and NfHSMI35) were analysed using ELISA technique. A putative index of ‘axonal health’ was expressed as a ratio of NfHSMI34 to NfHSMI35. NfHSMI34 and the NfHSMI34:SMI35 were significantly elevated in subjects with O N compared to controls. No significant differences in levels of C SF BSP were seen between O N subjects with C DMS plus those at high risk of progression to MS and O N subjects with normal MRI and negative C SF analysis. In conclusion, there is evidence of axonal damage in subjects who present with O N, which is independent of the diagnosis of C DMS.

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