Oral administration of a synthetic vinyl-ether plasmalogen normalizes open field activity in a mouse model of rhizomelic chondrodysplasia punctata.

Rhizomelic chondrodysplasia punctata (RCDP) is a rare genetic disorder caused by mutations in peroxisomal genes essential for plasmalogen biosynthesis. Plasmalogens are a class of membrane glycerophospholipids containing a vinyl-ether-linked fatty alcohol at the sn-1 position that affect functions including vesicular transport, membrane protein function and free radical scavenging. A logical rationale for the treatment of RCDP is therefore the therapeutic augmentation of plasmalogens.

Plasmalogen Augmentation Reverses Striatal Dopamine Loss in MPTP Mice.

Plasmalogens are a class of glycerophospholipids shown to play critical roles in membrane structure and function. Decreased plasmalogens are reported in the brain and blood of Parkinson's disease (PD) patients. The present study investigated the hypothesis that augmenting plasmalogens could protect striatal dopamine neurons that degenerate in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in mice, a PD model.

Pancreatic cancer serum biomarker PC-594: Diagnostic performance and comparison to CA19-9.

Aim: To investigate serum PC-594 fatty acid levels as a potential biomarker in North American pancreatic cancer (PaC) patients, and to compare its performance to CA19-9.

Methods: Using tandem mass spectrometry, we evaluated serum PC-594 levels from 84 North American patients with confirmed PaC and 99 cancer-free control subjects. We determined CA19-9 levels by ELISA.

Metabolic system alterations in pancreatic cancer patient serum: potential for early detection.

Background: The prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection. New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality. The goal of this study was to find metabolic biomarkers associated with PC by using a comprehensive metabolomics technology to compare serum profiles of PC patients to healthy control subjects.

Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity.

Background: Circulating levels of novel long-chain hydroxy fatty acids (called GTAs) were recently discovered in the serum of healthy subjects which were shown to be reduced in subjects with colorectal cancer (CRC), independent of tumor burden or disease stage. The levels of GTAs were subsequently observed to exhibit an inverse association with age in the general population. The current work investigates the biological activity of these fatty acids by evaluating the effects of enriched human serum extracts on cell growth and inflammation.

Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study.

Background: Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is implicated in many age-related chronic diseases such as cardiovascular disease (CVD), Alzheimer's disease (AD), and cancer. In vitro and ex vivo cellular plasmalogen deficiency models have been shown to exhibit impaired intra- and extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and serum plasmalogen deficiencies have been linked to AD, CVD, and cancer.

Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection.

Background: There are currently no accurate serum markers for detecting early risk of colorectal cancer (CRC). We therefore developed a non-targeted metabolomics technology to analyse the serum of pre-treatment CRC patients in order to discover putative metabolic markers associated with CRC. Using tandem-mass spectrometry (MS/MS) high throughput MS technology we evaluated the utility of selected markers and this technology for discriminating between CRC and healthy subjects.

Peripheral ethanolamine plasmalogen deficiency: a logical causative factor in Alzheimer's disease and dementia.

Although dementia of the Alzheimer's type (DAT) is the most common form of dementia, the severity of dementia is only weakly correlated with DAT pathology. In contrast, postmortem measurements of cholinergic function and membrane ethanolamine plasmalogen (PlsEtn) content in the cortex and hippocampus correlate with the severity of dementia in DAT. Currently, the largest risk factor for DAT is age.