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Astrocytes are a group of cells with specific morphological and functional characteristics that vary in different regions of the brain. During postnatal development, astrocytes migrate to the regions of interest in the brain. Astrocytes interact with neurons to protect, support and maintain normal cellular homeostasis during physiological ageing of the central nervous system (CNS), including the brain, spinal cord and retina. Mature astrocytes retain most of the genes expressed in progenitor cells to keep their proliferative potential. In the last few decades, astrocytes have been reported to serve an important role in age-related neurodegenerative diseases..

Lipids represent a ubiquitous and structurally diverse biopolymer group, prevalent throughout the body. They are particularly abundant in the brain where they represent more than 50% of the brain's dry weight, and subserve essential structural and functional roles. As structural constituents of the plasma membranes of neurons and other brain cells, they contribute to neuronal membrane properties, including flexibility, permeability, lipid raft formation, and protein-lipid interactions, and physiological functions such as neuroplasticity and synaptic signaling. Many lipids are synthesized endogenously in peripheral organs such as liver and adipose tissue, and also in the central nervous system (CNS), while a few are essential dietary lipids. All have complex mechanisms of transport in plasma, where they are conveyed on carrier particles such as high- and low-density lipoprotein. In addition to their important structural roles, lipids and their metabolic derivatives such as isoprostanes, leukotrienes, prostaglandins, and endocannabinoids serve important signaling and molecular messenger roles, but can also reflect levels of oxidative stress or dysregulation in disease. In this review, we explore the diversity of lipid roles with a focus on brain function in the ageing CNS and dementia.

Owing to the global exponential increase in population ageing, there is an urgent unmet need to develop reliable strategies to slow down and delay the ageing process. Age-related neurodegenerative diseases are among the main causes of morbidity and mortality in our contemporary society and represent a major socio-economic burden. There are several controversial factors that are thought to play a causal role in brain ageing which are continuously being examined in experimental models. Among them are oxidative stress and brain inflammation which are empirical to brain ageing. Although some candidate drugs have been developed which reduce the ageing phenotype, their clinical translation is limited. There are several strategies currently in development to improve brain ageing. These include strategies such as caloric restriction, ketogenic diet, promotion of cellular nicotinamide adenine dinucleotide (NAD+) levels, removal of senescent cells, ‘young blood’ transfusions, enhancement of adult neurogenesis, stem cell therapy, vascular risk reduction, and non-pharmacological lifestyle strategies. Several studies have shown that these strategies can not only improve brain ageing by attenuating age-related neurodegenerative disease mechanisms, but also maintain cognitive function in a variety of pre-clinical experimental murine models. However, clinical evidence is limited and many of these strategies are awaiting findings from large-scale clinical trials which are nascent in the current literature. Further studies are needed to determine their long-term efficacy and lack of adverse effects in various tissues and organs to gain a greater understanding of their potential beneficial effects on brain ageing and health span in humans.

The kynurenine pathway (KP) is the principal route of L-Tryptophan (TRP) catabolism leading to the production of kynurenine (KYN), the neuroprotectants, kynurenic acid (KYNA) and picolinic acid (PIC), and the excitotoxic neurotoxin, quinolinic acid (QUIN). The enzymes indoleamine 2,3-dioxygenase-1 (IDO-1), indoleamine 2, 3-dioxygenase-2 (IDO-2) and tryptophan 2,3-dioxygenase (TDO-2) initiate the first step of the KP. Downstream enzymes include kynureninase (KYNU), 3-hydroxyanthranilate 3,4-dioxygenase (3-HAAO), kynurenine hydroxylase (KMO) and 2-amino-3-carboxymuconate semialdehyde decarboxylase (ACMSD). Kynurenine aminotransferase-I (KAT-I) is one of the enzymes responsible for synthesising KYNA. Mounting evidence directly implicates that IDO-1 induction in various tumours is a crucial mechanism facilitating tumour immune evasion and persistence. However, the involvement of the downstream machinery of the KP in brain tumour progression remains unexplored. A complete characterisation of the KP in brain tumours and the role of the KP in maintaining homeostasis between neuroprotection and neurodegeneration in glioma has not yet been investigated. Here we report the first comprehensive characterisation of the KP in cultured human glioma cells and GBM patient plasma. Our qRT-PCR data revealed that interferon-gamma (IFN-γ) (100 IU/ml) stimulation significantly potentiated the expression of IDO-1 IDO-2, KYNU, 3-HAAO, KMO and significantly down-regulated ACMSD and KAT-I expression in cultured human glioma cells. HPLC analysis revealed that IFN-γ stimulation significantly increased KP activity (KYN/TRP ratio), and significantly lowered the KYNA/KYN neuroprotective ratio in human cultured glioma cells. Our HPLC and GCMS data revealed that KP activation was significantly higher and the concentrations of TRP, KYNA, QUIN and PIC and the KYNA/KYN ratio were significantly lower in GBM patient plasma (n = 18) compared to controls. These results provide further evidence for the involvement of the KP in glioma pathophysiology and highlights a potential role of KP products as novel and highly attractive therapeutic targets to evaluate for the treatment of brain tumours.

Elevated levels of several kynurenine pathway (KP) metabolites, e.g. quinolinic acid (QUIN), have been implicated in the aetiology of several neurodegenerative diseases such as Alzheimer‟s disease (AD) and Multiple Sclerosis (MS). The end product of the KP is NAD+, an essential cofactor for energy metabolism. NAD+ also serves as the sole substrate for the DNA repair enzyme, poly(ADP-ribose) polymerase (PARP). More recently, NAD+ has been identified as an essential substrate for a new class of histone deacetylases known as SIRT1, which has been linked to longevity. Free radical mediated PARP activation and NAD+ depletion may contribute to brain aging and tissue damage in multiple brain disorders. Our results indicate a direct involvement of the KP in NAD+ synthesis in human brain cells, and that reduced intracellular NAD+ synthesis leads to reduced activity of NAD+ dependent histone deacetylase function. We show that the KP metabolite and NMDA receptor agonist, QUIN is a substrate of NAD+ synthesis in nanomolar concentrations in both astrocytes and neurons but is cytotoxic at higher amounts in both cell types. These results also show a clear neuroprotective effect of NMDA receptor antagonism and nitric oxide synthase inhibition against QUIN mediated neuronal and glial cytoxicity, strongly suggesting that QUIN-induced excitotoxicity in astrocytes and neurons is mediated by overactivation of the NMDA receptor. We also show that natural polyphenolic compounds can attenuate QUIN-mediated neurotoxicity by a number of mechanisms reported herein. We also provide evidence for the first time that tryptophan metabolism leading to NAD+ synthesis is unregulated in tissue obtained from aged female wistar rats. SIRT1 activity was also decreased and acetylated p53 increased in these same animals in response to an unregulated PARP-mediated NAD+ depletion. Consistent with these animal data we also found that human serum NAD+ levels are reduced in MS.

According to the World Health Organization, two billion people will be aged 60 years or older by 2050. Aging is a major risk factor for a number of neurodegenerative disorders. These age-related disorders currently represent one of the most important and challenging health problems worldwide. Therefore, much attention has been directed towards the design and development of neuroprotective agents derived from natural sources. These phytochemicals have demonstrated high efficacy and low adverse effects in multiple in vitro and in vivo studies. Among these phytochemicals, dietary flavonoids are an important and common chemical class of bioactive products, found in several fruits and vegetables. Luteolin is an important flavone, which is found in several plant products, including broccoli, pepper, thyme, and celery. Numerous studies have shown that luteolin possesses beneficial neuroprotective effects both in vitro and in vivo. Despite this, an overview of the neuroprotective effects of luteolin has not yet been accomplished. Therefore, the aim of this paper is to provide a review of the available literature regarding the neuroprotective effects of luteolin and its molecular mechanisms of action. Herein, we also review the available literature regarding the chemistry of luteolin, its herbal sources, and bioavailability as a pharmacological agent for the treatment and management of age-related neurodegenerative disorders.

Background Neurodegenerative diseases are increasingly inevitable as the population gets older, with enormous socio-economic costs. The World Health Organization (WHO) has reported that by 2040, neurodegenerative diseases will overtake cancer to become the second leading cause of death, after cardiovascular disease. Objective Herein, this review outlines the neuroprotective effects and clinical implications of ellagitannins, a class of hydrolysable tannins, for the management and treatment of neurodegenerative disorders. Results Recent investigations suggest that the combination of genes and environmental toxins may contribute to the risk of developing neurodegenerative disorders. Thus, intervention strategies aimed at reducing exposure to risk factors such as life style, smoking, diet, vitamin deficiencies, chemical exposure and pollution are warranted. Modulation of dietary components including ellagitannins, as a therapeutic strategy to slow down or attenuate the progression of neuronal degeneration has become a focus of interest in the last few decades. Conclusion Polyphenolic plant phytochemicals and ellagitannins in particular, contain an array of neuroprotective properties useful to improve human health and protect against neurodegeneration.

In the present paper, we will discuss on the importance of autophagy in the central nervous system, and outline the relation between autophagic pathways and the pathogenesis of neurodegenerative disorders. The potential therapeutic benefits of naturally occurring phytochemicals as pharmacological modulators of autophagy will also be addressed. Our findings provide renewed insight on the molecular modes of protection by polyphenols, which is likely to be at least in part mediated not only by their potent antioxidant and anti-inflammatory effects, but also through modulation of autophagic processes to remove the aberrant protein aggregates.

Green GABA (GGABA) and Oolong GABA (OGABA) teas are relatively new varieties of tea, whose chemical composition and functional properties are largely under-studied, despite their promising health capacities. Post stroke depression (PSD) is a complication of stroke with high clinical relevance, yielding increasing mortality and morbidity rates, and a lower response to common therapies and rehabilitation. Methods: Two chemically characterized commercial samples of GGABA and OGABA were investigated for effects on mood following oral administration using a mouse model of PSD, through common validated tests including the Despair Swimming Test and Tail Suspension Test. Moreover, the antioxidant activity of GGABA and OGABA was evaluated by determining the levels of lipid peroxidation products and the activity of antioxidant enzymes in the mouse brain in vivo. Results: GGABA and OGABA attenuated depressed mood by influencing behavioral parameters linked to depression. GGABA was more active than OGABA in this study, and this effect may be likely due to a higher content of polyphenolic substances and amino acids in GGABA compared to OGABA. GGABA also exerted a greater antioxidant activity. Conclusions: Our data suggests that GABA tea is a promising candidate that can be used as an adjuvant in the management of PSD., The authors would like to thank Patrizia Arcidiaco for her excellent support in the analysis of aminoacids and La Teiera Eclettica (Milan, Italy), for providing tea samples used in the present work. A. Sureda was supported by Instituto de Salud Carlos III, the Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, CIBEROBN (CB12/03/30038).