María Jesús Vega-Bello

Background and Objectives: The main neurodegenerative diseases (NDs)—Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS)—represent a growing global health burden with no available disease-modifying therapies. Curcumin, a polyphenol from Curcuma longa, is a promising candidate owing to its pleiotropic antioxidant, anti-inflammatory, and neuroprotective profile observed mainly in preclinical models, but the poor oral bioavailability (®, BCM-95^®, Longvida^®, and Theracurmin^®) to fourth-generation systems (biomimetic nanoparticles, MOFs, microneedles, 3D scaffolds, hydrogels, and carbon dots) that substantially increase the bioavailability in preclinical studies. Combination strategies, such as curcumin with resveratrol and dutasteride, show preliminary clinical signals in ALS. However, clinical translation remains limited: over 80% of positive animal findings have not been replicated in humans, formulation characterization is frequently incomplete, and most trials lack CNS-exposure biomarkers. Importantly, most of the reported bioavailability claims are based on total curcumin measurements (parent aglycone plus its inactive Phase II conjugates) rather than the active aglycone alone, a methodological limitation that should be considered when interpreting the magnitude of the bioavailability improvements reported for novel formulations. Conclusions: Curcumin exhibits pleiotropic neuroprotective activity in preclinical models of AD, PD, MS, and ALS, mediated by interconnected antioxidant, anti-inflammatory, anti-amyloidogenic, mitochondrial, and gut–brain axis mechanisms. However, its poor systemic bioavailability (<1%), minimal blood–brain barrier penetration, and extensive first-pass metabolism have limited clinical translation. Advanced drug delivery systems (including lipid-based carriers (liposomes, solid lipid nanoparticles, and nanostructured lipid carriers), polymeric nanoparticles (PLGA and chitosan), and bioinspired vesicles (exosomes)) are essential in order to overcome these barriers. Nevertheless, the formulation heterogeneity, limited long-term safety data, and reliance on preclinical models remain major obstacles; a definitive clinical translation will therefore require well-characterized formulations validated in phase II/III trials with cerebrospinal fluid exposure biomarkers, the pharmacokinetic monitoring of active aglycone (rather than total curcumin including inactive conjugates), and adaptive trial designs in neurological populations.

Background/Objectives: The main neurodegenerative diseases (NDs) - Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) - represent a growing global health burden with no available disease-modifying therapies. Curcumin, a polyphenol from Curcuma longa, is a promising candidate owing to its pleiotropic antioxidant, anti-inflammatory, and neuroprotective profile, but its oral bioavailability (<1%) and blood-brain barrier (BBB) penetration (<0.1%) severely limit its clinical application. The objective of this work was to critically examine the therapeutic potential of curcumin in NDs, focusing on advanced drug delivery systems (DDS) designed to overcome its pharmacokinetic barriers. Methods: Narrative, non-systematic review of PubMed/MEDLINE, Scopus, and Web of Science, structured around five areas: molecular mechanisms, pharmacokinetic barriers, evolution of DDS, disease-specific applications, and translational limitations. Results: Curcumin exhibits neuroprotective activity in preclinical models of the four NDs analysed, acting on six interconnected mechanisms and the gut-brain axis. Four generations of DDS have been developed, from phytosomes and clinically used lipid dispersions (Meriva®, BCM-95®, Longvida®, Theracurmin®) to fourth-generation systems (biomimetic nanoparticles, MOFs, microneedles, 3D scaffolds, hydrogels, carbon dots) that substantially increase bioavailability in preclinical studies. Combination strategies, such as curcumin with resveratrol and dutasteride, show preliminary clinical signals in ALS. However, clinical translation remains limited: over 80% of positive animal findings have not been replicated in humans, formulation characterization is frequently incomplete, and most trials lack CNS-exposure biomarkers. Conclusions: DDS are essential to unlock curcumin’s therapeutic potential in neurology, but its clinical translation requires phase II/III trials with well-characterized formulations, cerebrospinal fluid exposure biomarkers, and adaptive designs.

Intermittent fasting (IF) is a dietary approach that has gained popularity in recent years. More and more Spanish people are following this eating pattern, which consists of alternating periods of fasting with periods of food intake. Its benefits include improved metabolic and vascular health and weight loss. Objectives: 1. To study the prevalence of IF among the Spanish population. 2. To explore how demographic factors influence the choice to adopt this dietary approach. Methods: A descriptive cross-sectional study was conducted on the Spanish population using the NutSo-HH questionnaire, which was constructed, validated, and disseminated by the research team through a non-probabilistic snowball sampling approach, collecting socio-demographic data and nutritional, social and lifestyle habits of the population. Results and conclusions: A valid sample of 22,181 people participated, of whom 4.59% (n = 1018) said they practiced IF. The data show that more middle-aged men than women practice IF. In addition, individuals who follow IF methods are less likely to have no control over their food intake, are less scared to gain weight and have a higher body image, but no differences were found related to unhealthy food and nights out. There were also no significant differences in terms of the level of education, income, size of municipality, or region of residence. In conclusion, a person who practices IF seems to have adopted a healthier lifestyle and social habits.

Amyotrophic lateral sclerosis (ALS) is a chronic and progressive neurodegenerative disease that leads to the loss of motor neurons. The dietary intake of ALS patients is thought to influence the prognosis and progression of the disease. The aim of this study was to examine the nutritional, clinical and sociodemographic characteristics of ALS patients in Spain. A cross-sectional descriptive study with demographics, clinical anamnesis and anthropometric assessment was carried out. Nutritional intake was recorded and compared with dietary reference intakes (DRI). Forty subjects (25 males; 15 females) aged 54.7 ± 10.17 were included in the study. The mean weight and height were 67.99 ± 8.85 kg and 167.83 ± 8.79 cm, respectively. Clinical phenotype, time to diagnosis, year of onset and family history were not associated with the place of origin. Clinical phenotype had no influence on time of diagnosis. Caloric and protein intakes were adequate, while carbohydrate, vitamin B8 and iodine intakes were significantly lower than the DRI. Lipids; vitamins B1, B2, B3, B5, B6, B12, C and E; sodium; phosphorus; and selenium intakes were significantly higher than the recommended nutritional standards. ALS patients, who are homogeneously distributed throughout our national territory, should modify their dietary habits to minimize ultra-processed products and prioritize foods rich in healthy fats and fiber.

Background: Lichens are complex symbiotic associations between a fungus and an alga or cyanobacterium. Due to their great adaptability to the environment, they have managed to colonize many terrestrial habitats, presenting a worldwide distribution from the poles to the tropical regions and from the plains to the highest mountains. In the flora of the Antarctic region, lichens stand out due to their variety and development and are a potential source of new bioactive compounds. Methods: A phytochemical study of the Antarctic lichen Usnea aurantiaco-atra (Jacq) Bory was conducted with the intention of determining the most important metabolites. In addition, the cytotoxic and antioxidant activities of its extracts were determined. Results: Cytotoxicity studies revealed that the hexane extract contains usnic acid as a majority metabolite, in addition to linoleic acid, ergosterols and terpenes, and demonstrates cytotoxic activity against an A375 melanoma cell line. On the other hand, the presence of total phenols in the extracts did not influence their antioxidant activity. Conclusions: U. aurantiaco-atra contains mainly usnic acid, although there are terpenes and ergosta compounds that could be responsible for its cytotoxic activity. The presence of phenols did not confer antioxidant properties.

ABSTRACT Lichens are complex symbiotic associations between a fungus (mycobiont) and photobiont, which can be either an alga or cyanobacteria. They are proven as the earliest colonizers of terrestrial habitats on the earth with a worldwide distribution from the Poles to tropical regions and from the plains to the highest mountains. In this study, the antartic lichen Usnea aurantiaco-atra has been characterized morphologically as well as structurally. A phytochemical study has been carried out, aiming to explore the most important metabolites. Moreover, the cytotoxic, antioxidant and insecticidal activity of their extracts has been determined. Citotoxicity studies have found that the hexanic extract that contains usnic acid as its main metabolite, linoleic acid and terpenes proved to have an interesting citotoxic activity when compared to melanoma and queratinocites. Testing the extract’s insecticidal activity in Ceratitis Capitata has demonstrated that usnic acid is linked to flies’ mortality. However, the results obtained with different extracts cannot be considered significant. On another note, we have analyzed the presence of total phenols in the extracts and we have seen that they do not have a significant influence in their antioxidant activity.