Aging-Associated Amyloid-β Plaques and Neuroinflammation in Bottlenose Dolphins (Tursiops truncatus) and Novel Cognitive Health-Supporting Roles of Pentadecanoic Acid (C15:0) DOI Open Access
Stephanie Venn‐Watson, Eric D. Jensen

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3746 - 3746

Опубликована: Апрель 16, 2025

There is an urgent need to identify interventions that broadly target aging-related cognitive decline and progression Alzheimer’s disease (AD). Bottlenose dolphins (Tursiops truncatus) have histologic changes similar AD in humans, they also develop shared age-associated co-morbidities identified as risk factors for including type 2 diabetes, ferroptosis, iron overload, which can be driven by nutritional C15:0 deficiency. We hypothesized (1) would amyloid beta (Aβ) plaques neuroinflammation paralleled of humans relation age-related progression, quantitative concentration, brain region; (2) dose-dependent activities relevant protecting health. Quantitative immunohistochemistry staining was used assess 68 tissues from archived brains 19 Navy evaluate associations among region, sex, age group. Further, activities, using a third-party panel intended screen potential therapeutics, were evaluated. Similar had the highest Aβ plaque density variation hippocampus (90th percentile 4.95 plaques/mm2), where increased with (p = 0.05). All measured markers detected, concentrations activated microglia (CD68+) (0.46 ± 0.38 cells/mm2). inhibitor two targets, fatty acid amide hydrolase (FAAH) (IC50 2.5 µM, 89% maximum inhibition at 50 µM relative URB597) monoamine oxidase B (MAO-B) 19.4 70% R(-)-Deprenyl). These demonstrated efficacy against formation neuroinflammation, protection function hippocampus. findings suggest that, addition co-morbidities, may play distinct role supporting health, especially higher concentrations.

Язык: Английский

Anxiety Disorders: Treatments, Models, and Circuitry Mechanisms DOI Creative Commons
Li Ren,

Yue Fan,

Wenjian Wu

и другие.

European Journal of Pharmacology, Год журнала: 2024, Номер 983, С. 176994 - 176994

Опубликована: Сен. 12, 2024

Язык: Английский

Процитировано

6
Discovery of MAGL Inhibition by Lophine Derivatives: An Unexpected Finding from Chemiluminescent Assay Development DOI Creative Commons
Roberta Ottria, Silvana Casati, Ornella Xynomilakis

и другие.

Molecules, Год журнала: 2025, Номер 30(7), С. 1605 - 1605

Опубликована: Апрель 3, 2025

The inhibitory effects of two novel lophine derivatives were unexpectedly discovered during the development a chemiluminescent monoacylglycerol lipase (MAGL) assay. proposed found to exhibit concentration-dependent on MAGL with octanoic and palmitic acid esters 2-(4-hydroxyphenyl)-4,5-diphenylimidazole showing strongest activity. Reversibility assays using fluorometric method confirmed that these compounds interact in stable, irreversible manner. To further investigate their mode interaction, docking studies performed, supporting hypothesis 3 4 may act as competitive inhibitors. Lophine initially designed synthesized potential chemiluminescence pro-enhancers. However, assay optimization revealed no signal production upon hydrolysis, precluding use probes. These findings suggest is promising candidate for inhibitors, although needed enhance binding affinity selectivity.

Язык: Английский

Процитировано

0
FAAH Modulators from Natural Sources: A Collection of New Potential Drugs DOI Creative Commons

Catalin Nicoara,

Filomena Fezza, Mauro Maccarrone

и другие.

Cells, Год журнала: 2025, Номер 14(7), С. 551 - 551

Опубликована: Апрель 5, 2025

The endocannabinoid system (ECS) plays a crucial role in maintaining homeostasis by regulating immune response, energy metabolism, cognitive functions, and neuronal activity. It consists of endocannabinoids (eCBs), cannabinoid receptors (CBRs), enzymes involved eCB biosynthesis degradation. Increasing evidence highlights the involvement ECS under several pathological conditions, making it promising therapeutic target. Recent research efforts have focused on modulating endogenous levels, particularly through inhibition fatty acid amide hydrolase (FAAH), main catabolic enzyme major anandamide. Natural substances, including plant extracts purified compounds, can inhibit FAAH represent area pharmacological research. inhibitors are attractive due to their potentially lower toxicity compared synthetic them safer candidates for applications. Phytocannabinoids, flavonoids, flavolignans been shown efficiently FAAH. structural diversity bioactivity these natural substances provide valuable alternative inhibitors, may open new avenues developing innovative tools.

Язык: Английский

Процитировано

0
Aging-Associated Amyloid-β Plaques and Neuroinflammation in Bottlenose Dolphins (Tursiops truncatus) and Novel Cognitive Health-Supporting Roles of Pentadecanoic Acid (C15:0) DOI Open Access
Stephanie Venn‐Watson, Eric D. Jensen

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3746 - 3746

Опубликована: Апрель 16, 2025

There is an urgent need to identify interventions that broadly target aging-related cognitive decline and progression Alzheimer’s disease (AD). Bottlenose dolphins (Tursiops truncatus) have histologic changes similar AD in humans, they also develop shared age-associated co-morbidities identified as risk factors for including type 2 diabetes, ferroptosis, iron overload, which can be driven by nutritional C15:0 deficiency. We hypothesized (1) would amyloid beta (Aβ) plaques neuroinflammation paralleled of humans relation age-related progression, quantitative concentration, brain region; (2) dose-dependent activities relevant protecting health. Quantitative immunohistochemistry staining was used assess 68 tissues from archived brains 19 Navy evaluate associations among region, sex, age group. Further, activities, using a third-party panel intended screen potential therapeutics, were evaluated. Similar had the highest Aβ plaque density variation hippocampus (90th percentile 4.95 plaques/mm2), where increased with (p = 0.05). All measured markers detected, concentrations activated microglia (CD68+) (0.46 ± 0.38 cells/mm2). inhibitor two targets, fatty acid amide hydrolase (FAAH) (IC50 2.5 µM, 89% maximum inhibition at 50 µM relative URB597) monoamine oxidase B (MAO-B) 19.4 70% R(-)-Deprenyl). These demonstrated efficacy against formation neuroinflammation, protection function hippocampus. findings suggest that, addition co-morbidities, may play distinct role supporting health, especially higher concentrations.

Язык: Английский

Процитировано

0