Signaling Mechanisms of Selective PPARγ Modulators in Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. The continuous increase in the incidence of AD with the aged population and mortality rate indicates the urgent need for establishing novel molecular targets for therapeutic potential. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists such as rosiglitazone and pioglitazone reduce amyloid and tau pathologies, inhibit neuroinflammation, and improve memory impairments in several rodent models and in humans with mild-to-moderate AD. However, these agonists display poor blood brain barrier permeability resulting in inadequate bioavailability in the brain and thus requiring high dosing with chronic time frames. Furthermore, these dosing levels are associated with several adverse effects including increased incidence of weight gain, liver abnormalities, and heart failure. Therefore, there is a need for identifying novel compounds which target PPARγ more selectively in the brain and could provide therapeutic benefits without a high incidence of adverse effects. This review focuses on how PPARγ agonists influence various pathologies in AD with emphasis on development of novel selective PPARγ modulators

Maternal Dietary Patterns and Gestational Diabetes Risk: A Case-Control Study

Background. Maternal dietary patterns play an important role in the progress of gestational diabetes mellitus (GDM). The aim of the present study was to explore this association. Method. A total of 388 pregnant women (122 case and 266 control) were included. Dietary intake were collected using a food frequency questionnaire (FFQ). GDM was diagnosed using a 100-gram, 3-hour oral glucose tolerance test. Dietary pattern was identified by factor analysis. To investigate the relation between each of the independent variables with gestational diabetes, the odds ratio (OR) was calculated. Results. Western dietary pattern was high in sweets, jams, mayonnaise, soft drinks, salty snacks, solid fat, high-fat dairy products, potatoes, organ meat, eggs, red meat, processed foods, tea, and coffee. The prudent dietary pattern was characterized by higher intake of liquid oils, legumes, nuts and seeds, fruits and dried fruits, fish and poultry whole, and refined grains. Western dietary pattern was associated with increased risk of gestational diabetes mellitus before and after adjustment for confounders (OR = 1.97, 95% CI: 1.27–3.04, OR = 1.68, 95% CI: 1.04–2.27). However, no significant association was found for a prudent pattern. Conclusion. These findings suggest that the Western dietary pattern was associated with an increased risk of GDM