Plasmalogens as a marker of elevated systemic oxidative stress in Parkinson's disease

Dragonas, Charalampos; Bertsch, Thomas; Sieber, Cornel; Brosche, Thorolf

doi:10.1515/cclm.2009.205

Cited by 50 publications

(38 citation statements)

References 12 publications

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“…Therefore any therapeutic intervention aimed at restoring ether-phospholipid levels should have a beneficial effect. In recent years deficiencies in plasmalogen levels have been observed in other peroxisomal diseases as well as non-peroxisomal disorders [49]–[52], which increases the need for the development and implementation of a method to increase plasmalogen levels.…”

Section: Discussionmentioning

confidence: 99%

Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice

et al. 2011

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A deficiency of plasmalogens, caused by impaired peroxisomal metabolism affects normal development and multiple organs in adulthood. Treatment options aimed at restoring plasmalogen levels may be relevant for the therapy of peroxisomal and non-peroxisomal disorders. In this study we determined the in vivo efficacy of an alkyl glycerol (AG), namely, 1-O-octadecyl-rac-glycerol, as a therapeutic agent for defects in plasmalogen synthesis. To achieve this, Pex7 knockout mice, a mouse model for Rhizomelic Chondrodysplasia Punctata type 1 characterized by the absence of plasmalogens, and WT mice were fed a control diet or a diet containing 2% alkyl-glycerol. Plasmalogen levels were measured in target organs and the biochemical data were correlated with the histological analysis of affected organs. Plasmalogen levels in all peripheral tissues of Pex7 KO mice fed the AG diet for 2 months normalized to the levels of AG fed WT mice. In nervous tissues of Pex7 KO mice fed the AG-diet, plasmalogen levels were significantly increased compared to control fed KO mice. Histological analysis of target organs revealed that the AG-diet was able to stop the progression of the pathology in testis, adipose tissue and the Harderian gland. Interestingly, the latter tissues are characterized by the presence of lipid droplets which were absent or reduced in size and number when ether-phospholipids are lacking, but which can be restored with the AAG treatment. Furthermore, nerve conduction in peripheral nerves was improved. When given prior to the occurrence of major pathological changes, the AG-diet prevented or ameliorated the pathology observed in Pex7 KO mice depending on the degree of plasmalogen restoration. This study provides evidence of the beneficial effects of treating a plasmalogen deficiency with alkyl-glycerol.

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Section: Discussionmentioning

confidence: 99%

Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice

et al. 2011

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“…One speculated reason for this might be mitochondrial dysfunction in cerebral and peripheral tissues. However since the differences are small and inter-individual variability seems to be high, plasmalogens do not seem to be a suitable marker for the prediction of disease development (Dragonas et al, 2009). Interestingly there is a pathophysiological link between PD and dementia, since with disease progression some patients with PD develop fronto-temporal type dementia (Aarsland et al, 2001;Buter et al, 2008).…”

Section: Parkinson's Diseasementioning

confidence: 99%

Plasmalogens the neglected regulatory and scavenging lipid species

Wallner

Schmitz

2011

Chemistry and Physics of Lipids

275

243

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“…Since circulating plasmalogens are decreased in a number of other clinical conditions, the effects of these potential confounds need to be addressed in future AD studies. These include plasmalogen decrements in ischemic cerebrovascular disease [23], Parkinson's disease [24], hypertension [25], uremia [26], and hyperlipidemia [27]. …”

Section: Glycerophospholipidsmentioning

confidence: 99%

Lipidomics of Alzheimer's disease: current status

Wood

2012

Alzheimers Res Ther

138

142

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Alzheimer's disease (AD) is a cognitive disorder with a number of complex neuropathologies, including, but not limited to, neurofibrillary tangles, neuritic plaques, neuronal shrinkage, hypomyelination, neuroinflammation and cholinergic dysfunction. The role of underlying pathological processes in the evolution of the cholinergic deficit responsible for cognitive decline has not been elucidated. Furthermore, generation of testable hypotheses for defining points of pharmacological intervention in AD are complicated by the large scale occurrence of older individuals dying with no cognitive impairment despite having a high burden of AD pathology (plaques and tangles). To further complicate these research challenges, there is no animal model that reproduces the combined hallmark neuropathologies of AD. These research limitations have stimulated the application of 'omics' technologies in AD research with the goals of defining biologic markers of disease and disease progression and uncovering potential points of pharmacological intervention for the design of AD therapeutics. In the case of sporadic AD, the dominant form of dementia, genomics has revealed that the ε4 allele of apolipoprotein E, a lipid transport/chaperone protein, is a susceptibility factor. This seminal observation points to the importance of lipid dynamics as an area of investigation in AD. In this regard, lipidomics studies have demonstrated that there are major deficits in brain structural glycerophospholipids and sphingolipids, as well as alterations in metabolites of these complex structural lipids, which act as signaling molecules. Peroxisomal dysfunction appears to be a key component of the changes in glycerophospholipid deficits. In this review, lipid alterations and their potential roles in the pathophysiology of AD are discussed.

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Plasmalogens as a marker of elevated systemic oxidative stress in Parkinson's disease

Cited by 50 publications

References 12 publications

Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice

Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice

Plasmalogens the neglected regulatory and scavenging lipid species

Lipidomics of Alzheimer's disease: current status

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