Forest Biomass as a Promising Source of Bioactive Essential Oil and Phenolic Compounds for Alzheimer's Disease Therapy.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people worldwide. Currently, there are no effective treatments for AD able to prevent disease progression, highlighting the urgency of finding new therapeutic strategies to stop or delay this pathology. Several plants exhibit potential as source of safe and multi-target new therapeutic molecules for AD treatment. Meanwhile, Eucalyptus globulus extracts revealed important pharmacological activities, namely antioxidant and anti-inflammatory properties, which can contribute to the reported neuroprotective effects. This review summarizes the chemical composition of essential oil (EO) and phenolic extracts obtained from Eucalyptus globulus leaves, disclosing major compounds and their effects on AD-relevant pathological features, including deposition of amyloid-ß (Aß) in senile plaques and hyperphosphorylated tau in neurofibrillary tangles (NFTs), abnormalities in GABAergic, cholinergic and glutamatergic neurotransmission, inflammation, and oxidative stress. In general, 1,8-cineole is the major compound identified in EO, and ellagic acid, quercetin, and rutin were described as main compounds in phenolic extracts from Eucalyptus globulus leaves. EO and phenolic extracts, and especially their major compounds, were found to prevent several pathological cellular processes and to improve cognitive function in AD animal models. Therefore, Eucalyptus globulus leaves are a relevant source of biological active and safe molecules that could be used as raw material for nutraceuticals and plant-based medicinal products useful for AD prevention and treatment.

Endoplasmic Reticulum-Mitochondria Contacts Modulate Reactive Oxygen Species-Mediated Signaling and Oxidative Stress in Brain Disorders: The Key Role of Sigma-1 Receptor.

Significance: Mitochondria-Associated Membranes (MAMs) are highly dynamic endoplasmic reticulum (ER)-mitochondria contact sites that, due to the transfer of lipids and Ca2+ between these organelles, modulate several physiologic processes, such as ER stress response, mitochondrial bioenergetics and fission/fusion events, autophagy, and inflammation. In addition, these contacts are implicated in the modulation of the cellular redox status since several MAMs-resident proteins are involved in the generation of reactive oxygen species (ROS), which can act as both signaling mediators and deleterious molecules, depending on their intracellular levels. Recent Advances: In the past few years, structural and functional alterations of MAMs have been associated with the pathophysiology of several neurodegenerative diseases that are closely associated with the impairment of several MAMs-associated events, including perturbation of the redox state on the accumulation of high ROS levels. Critical Issues: Inter-organelle contacts must be tightly regulated to preserve cellular functioning by maintaining Ca2+ and protein homeostasis, lipid metabolism, mitochondrial dynamics and energy production, as well as ROS signaling. Simultaneously, these contacts should avoid mitochondrial Ca2+ overload, which might lead to energetic deficits and deleterious ROS accumulation, culminating in oxidative stress-induced activation of apoptotic cell death pathways, which are common features of many neurodegenerative diseases. Future Directions: Given that Sig-1R is an ER resident chaperone that is highly enriched at the MAMs and that controls ER to mitochondria Ca2+ flux, as well as oxidative and ER stress responses, its potential as a therapeutic target for neurodegenerative diseases such as Amyotrophic Lateral Sclerosis, Alzheimer, Parkinson, and Huntington diseases should be further explored. Antioxid. Redox Signal. 37, 758-780.

Chemical Composition and Effect against Skin Alterations of Bioactive Extracts Obtained by the Hydrodistillation of Eucalyptus globulus Leaves.

Eucalyptus globulus is planted extensively for pulp, paper and wood production. Although bioactive compounds obtained from its biomass are used as cosmetics ingredients, the skin effects were not yet fully explored. In order to fill this gap, this work aimed to study the protective effect against skin damage provided by the essential oil (EO) obtained from the hydrodistillation of Eucalyptus globulus leaves, and by an extract obtained from the hydrodistillation residual water (HRW). The major compound identified in the EO was 1,8-Cineole, and the phenolic acids in the HRW included gallic acid as the main phenolic constituent. Moreover, non-toxic EO and HRW concentrations were shown to have anti-aging skin effects in vitro, decreasing age-related senescence markers, namely ß-galactosidase and matrix metalloproteinases activation, as well as collagen type 1 upregulation. In addition, EO and HRW were found to exhibit depigmenting effects by inhibiting tyrosinase and melanin production, along with potent anti-inflammatory properties. Furthermore, the absence of skin irritation and sensitization in cells exposed to EO and HRW revealed the safety of both extracts for topical use. Taken together, these results highlight the beneficial effects of extracts obtained from Eucalyptus globulus biomass for skin aesthetic and health purposes, which should be explored deeply for the prediction of future pharmaceutical and dermocosmetics industrial applications.

APOEɛ4-TOMM40L Haplotype Increases the Risk of Mild Cognitive Impairment Conversion to Alzheimer's Disease.

BACKGROUND: Mild cognitive impairment (MCI) has been considered as a pre-dementia stage, although the factors leading to Alzheimer's disease (AD) conversion remain controversial. OBJECTIVE: Evaluate whether TOMM40 poly-T (TOMM40' 523) polymorphism is associated with the risk and conversion time from MCI to AD and secondly with AD cerebrospinal fluid (CSF) biomarkers, disentangling the APOE genotype. METHODS: 147 AD patients, 102 MCI patients, and 105 cognitively normal controls were genotyped for poly-T polymorphism. MCI patients were subdivided into two groups, the group of patients that converted to AD (MCI-AD) and the group of those that remained stable (MCI-S). RESULTS: TOMM40' 523 L allele was significantly more frequent in the MCI-AD group and having at least one L allele significantly increased the risk of conversion from MCI to AD (OR = 8.346, p < 0.001, 95% CI: 2.830 to 24.617). However, when adjusted for the presence of APOEɛ4 allele, both the L allele and ɛ4 allele lost significance in the model (p > 0.05). We then analyzed the APOEɛ4-TOMM40' 523 L haplotype and observed that patients carrying this haplotype had significantly higher risk (OR = 5.83; 95% CI = 2.30-14.83) and mean lower times of conversion to AD (p = 0.003). This haplotype was also significantly associated with a biomarker profile compatible with AD (p = 0.007). CONCLUSION: This study shows that the APOEɛ4-TOMM40' 523 L haplotype is associated with a higher risk and shorter times of conversion from MCI to AD, possibly driven by CSF biomarkers and mitochondrial dysfunction.

Calcium Signaling in Aging and Neurodegenerative Diseases 2019.

The European Calcium Society (ECS) workshop, which is held every 2 years, is a dedicated meeting of scientists interested in the elucidation of the action of calcium binding, calcium signaling and the study of proteins and organelles, such as mitochondria and endoplasmic reticulum, thereby involved, either in health and disease conditions. The 8th edition of the ECS workshop was organized by a group of researchers from the University of Coimbra, Portugal, in close collaboration with ECS board members. Thanks to the central role of "Calcium Signaling in Aging and Neurodegenerative Disorders", the ECS 2019 workshop was attended by 62 experts who presented their results in a plenary lecture and five regular symposia, two oral communication sessions and two poster sessions, followed by a hands-on session on calcium imaging. All the scientific and social events were fully participated by the scientific community that allowed a close and fruitful interaction and discussion between junior researchers and senior experts in the field. In this report, the contributions in individual sessions are summarized.