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Obesity and metabolic disorders can be risk factors for the onset and development of neurodegenerative diseases. The aim of the present study was to investigate the protective effects of a natural dietary supplement (NDS), containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin, on dysmetabolism and neurodegeneration in the brains of high fat diet (HFD)-fed mice. Decrease in the expression of FACL-4, CerS-1, CerS-4, cholesterol concentration and increase in the insulin receptor expression and insulin signaling activation, were found in brains of NDS-treated HFD brains in comparison with HFD untreated-mice, suggesting that NDS is able to prevent brain lipid accumulation and central insulin resistance. In the brains of NDS-treated HFD mice, the levels of RNS, ROS and lipid peroxidation, the expression of p-ERK, H-Oxy, i-NOS, HSP60, NF-kB, GFAP, IL-1β, IL-6 and CD4 positive cell infiltration were lower than in untreated HFD mice, suggesting antioxidant and anti-inflammatory effects of NDS. The decreased expression of p-ERK and GFAP in NDS-treated HFD mice was confirmed by immunofluorescence. Lastly, a lower number of apoptotic nuclei was found in cortical sections of NDS-treated HFD mice. The present data indicate that NDS exerts neuroprotective effects in HFD mice by reducing brain fat accumulation, oxidative stress and inflammation and improving brain insulin resistance.

Neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of neurodegenerative diseases characterized by cognitive and motor decline, epilepsy, visual loss and by lysosomal autofluorescent inclusions. Two distinct clinical phenotypes, the progressive epilepsy with mental retardation (EPMR) and a late-infantile variant of NCLs (CLN8-vLINCL) are associated with mutations in the CLN8 gene that encodes a transmembrane protein predominantly located to the endoplasmic reticulum (ER). To gain insight into the function of CLN8 protein, we employed the split-ubiquitin membrane-based yeast two-hybrid (MYTH) system, which detects protein-protein interactions in a membrane environment, using the full-length human CLN8 as bait and a human brain cDNA library as prey. We identified several potential protein partners of CLN8 and especially referred to VAPA, c14orf1/hERG28, STX8, GATE16, BNIP3 and BNIP3L proteins that are associated with biologically relevant processes such as synthesis and transport of lipids, vesicular/membrane trafficking, autophagy/mitophagy and apoptosis. Interactions of CLN8 with VAPA and GATE16 were further validated by co-immunoprecipitation and co-localization assays in mammalian cells. Using a new C-terminal-oriented CLN8 antibody, CLN8-VAPA interaction was also confirmed by co-staining in close spatial proximity within different CNS tissues. The results of this study shed light on potential interactome networks of CLN8 and provide a powerful starting point for understanding protein function(s) and molecular aspects of diseases associated with CLN8 deficiency.

Cyanobacteria have been recognized as a source of bioactive molecules to be employed in nutraceuticals, pharmaceuticals, and functional foods. An extract of Aphanizomenon flos-aquae (AFA), commercialized as Klamin®, was subjected to chemical analysis to determine its compounds. The AFA extract Klamin® resulted to be nontoxic, also at high doses, when administered onto LAN5 neuronal cells. Its scavenging properties against ROS generation were evaluated by using DCFH-DA assay, and its mitochondrial protective role was determined by JC-1 and MitoSOX assays. Klamin® exerts a protective role against beta amyloid- (Aβ-) induced toxicity and against oxidative stress. Anti-inflammatory properties were demonstrated by NFβB nuclear localization and activation of IL-6 and IL-1β inflammatory cytokines through ELISA. Finally, by using thioflavin T (ThT) and fluorimetric measures, we found that Klamin® interferes with Aβ aggregation kinetics, supporting the formation of smaller and nontoxic structures compared to toxic Aβ aggregates alone. Altogether, these data indicate that the AFA extract may play a protective role against mechanisms leading to neurodegeneration.

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Obesity has been associated with neurodegeneration and cognitive dysfunctions. Recent data showed that pistachio consumption is able to prevent and ameliorate dyslipidemia, hepatic steatosis, systemic and adipose tissue inflammation in mice fed a high-fat diet (HFD). The present study investigated the neuroprotective effects of pistachio intake in HFD mice. Three groups of mice were fed a standard diet (STD), HFD, or HFD supplemented with pistachio (HFD-P) for 16 weeks. Metabolic parameters (oxidative stress, apoptosis, and mitochondrial dysfunction) were analyzed by using specific assays and biomarkers. The pistachio diet significantly reduced the serum levels of triglycerides and cholesterol in the HFD model. No difference was observed in the index of insulin resistance between HFD and HFD-P. A higher number of fragmented nuclei were found in HFD cerebral cortex compared to STD and HFD-P. A decrease in reactive oxygen species, singlet oxygen and phosphorylated extracellular signal-regulated kinase, and an increase of superoxide dismutase 2 and heme oxygenase expression were found in the brains of the HFD-P samples compared to HFD. Furthermore, the impaired mitochondrial function found in HFD brain was partially recovered in HFD-P mice. These results suggest that the regular intake of pistachio may be useful in preventing obesity-related neurodegeneration, being able to reduce both metabolic and cellular dysfunctions.The positive effects of the Mediterranean diet on health have been well documented [9,10]. The longevity of one Mediterranean population, over 90 years old without dementia, was attributed to the nutraceutical components of the Mediterranean diet [11]. Functional food has been reported to delay or inhibit neurodegeneration, suggesting their employment as an alternative therapeutic strategy for correlated diseases [12][13][14].Benefits of nut consumption (mainly pistachios, walnuts, and almonds) have been described in studies on both animals and humans [15,16]. Daily nut consumption can improve dysmetabolic conditions such as obesity, type 2 diabetes, and related cardiovascular diseases [17,18]. In particular, Pistacia atlantica oleoresin has been proposed as an agent that protects the body against conditions associated with oxidative stress [19], including memory impairment, in lipopolysaccharide-treated rats [20]. Nevertheless, the potential beneficial impact of nut intake on neurodegenerative disorders, as well as on other cognitive-behavioral deficits, has been poorly explored.Compared to other nuts, pistachios possess a healthier nutritional profile, with low-fat content, high content of polyunsaturated fatty acids (13.3 g/100 g) and mono-unsaturated fatty acids (24.5 g/100 g), minerals (potassium, phosphorus, magnesium, and calcium) and vitamins (vitamin A, vitamin E, vitamin C, and vitamins B). Phytochemicals of pistachio show high bioavailability, contributing to the beneficial relationship between pistachio consumption and health-related outcomes [21]. Furthermore, recent data have demonstra...

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