Gender differences in white matter pathology and mitochondrial dysfunction in Alzheimer’s disease with cerebrovascular disease

Gallart‐Palau, Xavier; Lee, Benjamin Sian Teck; Adav, Sunil S.; Qian, Jingru; Serra, Aida; Park, Jung Eun; Lai, Mitchell K.P.; Chen, Christopher; Kalaria, Raj N.

doi:10.1186/s13041-016-0205-7

Cited by 53 publications

(44 citation statements)

References 79 publications

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“…In proteomic study of frontal cortex tissues from AD patients, Muller et al observed that disease-associated up-regulation of heat shock 70 kDa protein 1B and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is gender dependent [75]. Similarly, data from our own laboratory have revealed significant modulation of several redox proteins in the temporal lobe of Alzheimer’s disease with cerebrovascular diseases (AD-CVD) patients as well as sex-specific alterations in the white matter and mitochondrial proteome of female patients [55]. Proteomics findings of up-regulation of myelin proteolipid protein (PLP) and their enrichment in the temporal lobe of female AD-CVD was further validated by western blot techniques [55].…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, data from our own laboratory have revealed significant modulation of several redox proteins in the temporal lobe of Alzheimer’s disease with cerebrovascular diseases (AD-CVD) patients as well as sex-specific alterations in the white matter and mitochondrial proteome of female patients [55]. Proteomics findings of up-regulation of myelin proteolipid protein (PLP) and their enrichment in the temporal lobe of female AD-CVD was further validated by western blot techniques [55]. Proteomic analysis of AD-CVD brain tissues suggested that myelin basic protein (MBP) exhibited hyper-citrullination of arginine and deamidation of glutamine only in female patients (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…

Fig. 4Citrullination of arginine and deamidation of glutamine in myelin basic protein from female patients with AD-CVD (adapted from Gallart-Palau et al [55]) …”

Section: Introductionmentioning

confidence: 99%

“…When applied to the analysis of DPMs in complex biological samples, proteomic approaches provide unparallel power to assess the molecular basis of ‘proteinopathies’ such as dementia. Consequently, we now recognize that DPMs can promote pathological progression in human dementia by radically altering protein structure and function in the brain [45, 55]. There are several major types of DPM known to occur in human cells; deamidation, phosphorylation, nitrosylation, glycosylation, racemization, glycation, and hydroxylation, although these are not the only known modes of modification.…”

Section: Introductionmentioning

confidence: 99%

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Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling

Adav

2016

Mol Brain

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Dementia is a syndrome associated with a wide range of clinical features including progressive cognitive decline and patient inability to self-care. Due to rapidly increasing prevalence in aging society, dementia now confers a major economic, social, and healthcare burden throughout the world, and has therefore been identified as a public health priority by the World Health Organization. Previous studies have established dementia as a ‘proteinopathy’ caused by detrimental changes in brain protein structure and function that promote misfolding, aggregation, and deposition as insoluble amyloid plaques. Despite clear evidence that pathological cognitive decline is associated with degenerative protein modifications (DPMs) arising from spontaneous chemical modifications to amino acid side chains, the molecular mechanisms that promote brain DPMs formation remain poorly understood. However, the technical challenges associated with DPM analysis have recently become tractable due to powerful new proteomic techniques that facilitate detailed analysis of brain tissue damage over time. Recent studies have identified that neurodegenerative diseases are associated with the dysregulation of critical repair enzymes, as well as the misfolding, aggregation and accumulation of modified brain proteins. Future studies will further elucidate the mechanisms underlying dementia pathogenesis via the quantitative profiling of the human brain proteome and associated DPMs in distinct phases and subtypes of disease. This review summarizes recent developments in quantitative proteomic technologies, describes how these techniques have been applied to the study of dementia-linked changes in brain protein structure and function, and briefly outlines how these findings might be translated into novel clinical applications for dementia patients. In this review, only spontaneous protein modifications such as deamidation, oxidation, nitration glycation and carbamylation are reviewed and discussed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…

Fig. 4Citrullination of arginine and deamidation of glutamine in myelin basic protein from female patients with AD-CVD (adapted from Gallart-Palau et al [55]) …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling

Adav

2016

Mol Brain

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“…Recently, our group [43] applied discoverybased proteomics approach to evaluate gender differences in AD with cerebrovascular disease (CVD) subjects. Quantitative proteomics revealed gender-specific-altered mitochondriome.…”

Section: Quantitative Clinical Proteomics Of Brain Tissuementioning

confidence: 99%

Proteomic Study of Degenerative Protein Modifications in the Molecular Pathology of Neurodegeneration and Dementia

Adav¹,

Sze²

2016

Update on Dementia

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Dementia is a major public health burden, and the World Health Organization has identified this disorder as a major public health priority. There are limited treatment options due to poor understanding of key mechanism of dementia pathogenesis. Dementia has been regarded as a proteinopathy in which alterations of brain protein structure and function are the key features of the disorder. Proteinopathy can be triggered by degenerative protein modifications (DPMs), misfolding, aggregation, and deposition of the malformed proteins. Despite the clinical significance of alteration in protein abundances, DPMs, protein misfolding, and aggregation, the molecular mechanism that promotes these changes remains inadequately understood, mostly due to technical challenges. Proteomic is a powerful, sensitive, and advanced tool to study the progressive brain tissue damage that critically dysregulates key enzymes, accumulates modified proteins, and causes protein misfolding and aggregation, resulting in cognitive decline and dementia. The proteomic profiling of protein abundances and correlating DPMs with protein misfolding and aggregation have potential to elucidate underlying molecular mechanism of the disease. This chapter summarizes the recent proteomic developments for studying brain proteome, DPMs, and protein aggregation mechanism that may lead to dementia. We attempted to correlate DPMs and its impact on protein aggregation and deposition in brain tissues.

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Comparative iTRAQ‐Based Quantitative Proteomic Analysis of Pelteobagrus vachelli Liver under Acute Hypoxia: Implications in Metabolic Responses

Zhang

Wen

et al. 2017

Proteomics

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More and more frequently these days, aquatic ecosystems are being stressed by nutrient enrichment, pollutants, and global warming, leading to a serious depletion in oxygen concentrations. Although a sudden, significant lack of oxygen will result in mortality, fishes can have an acute behavior (e.g., an increase in breathing rate, reduction in swimming frequency) and physiology responses (e.g., increase in oxygen delivery, and reduction in oxygen consumption) to hypoxia, which allows them to maintain normal physical activity. Therefore, in order to shed further light on the molecular mechanisms of hypoxia adaptation in fishes, the authors conduct comparative quantitative proteomics on Pelteobagrus vachelli livers using iTRAQ. The research identifies 511 acute hypoxia-responsive proteins in P. vachelli. Furthermore, comparison of several of the diverse key pathways studied (e.g., peroxisome pathway, PPAR signaling pathway, lipid metabolism, glycolysis/gluco-neogenesis, and amino acid metabolism) help to articulate the different mechanisms involved in the hypoxia response of P. vachelli. Data from proteome analysis shows that P. vachelli can have an acute reaction to hypoxia, including detoxification of metabolic by-products and oxidative stress in light of continued metabolic activity (e.g., peroxisomes), an activation in the capacity of catabolism to get more energy (e.g., lipolysis and amino acid catabolism), a depression in the capacity of biosynthesis to reduce energy consumption (e.g., biosynthesis of amino acids and lipids), and a shift in the aerobic and anaerobic contributions to total metabolism. The observed hypoxia-related changes in the liver proteome of the fish can help to understand or can be related to the hypoxia-related response that takes place in similar conditions in the liver or other proteomes of mammals.

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Gender differences in white matter pathology and mitochondrial dysfunction in Alzheimer’s disease with cerebrovascular disease

Cited by 53 publications

References 79 publications

Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling

Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling

Proteomic Study of Degenerative Protein Modifications in the Molecular Pathology of Neurodegeneration and Dementia

Comparative iTRAQ‐Based Quantitative Proteomic Analysis of Pelteobagrus vachelli Liver under Acute Hypoxia: Implications in Metabolic Responses

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