-
1.
Effects of curcumin on mitochondria in neurodegenerative diseases.
Bagheri, H, Ghasemi, F, Barreto, GE, Rafiee, R, Sathyapalan, T, Sahebkar, A
BioFactors (Oxford, England). 2020;(1):5-20
Abstract
Neurodegenerative diseases (NDs) result from progressive deterioration of selectively susceptible neuron populations in different central nervous system (CNS) regions. NDs are classified in accordance with the primary clinical manifestations (e.g., parkinsonism, dementia, or motor neuron disease), the anatomic basis of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), and fundamental molecular abnormalities (e.g., mutations, mitochondrial dysfunction, and its related molecular alterations). NDs include the Alzheimer disease and Parkinson disease, among others. There is a growing evidence that mitochondrial dysfunction and its related mutations in the form of oxidative/nitrosative stress and neurotoxic compounds play major roles in the pathogenesis of various NDs. Curcumin, a polyphenol and nontoxic compound, obtained from turmeric, has been shown to have a therapeutic beneficial effect in various disorders especially on the CNS cells. It has been shown that curcumin has considerable neuro- and mitochondria-protective properties against broad-spectrum neurotoxic compounds and diseases/injury-associating NDs. In this article, we have reviewed the various effects of curcumin on mitochondrial dysfunction in NDs.
-
2.
Ferroptosis Is Regulated by Mitochondria in Neurodegenerative Diseases.
Zhou, J, Jin, Y, Lei, Y, Liu, T, Wan, Z, Meng, H, Wang, H
Neuro-degenerative diseases. 2020;(1):20-34
Abstract
BACKGROUND Neurodegenerative diseases are characterized by a gradual decline in motor and/or cognitive function caused by the selective degeneration and loss of neurons in the central nervous system, but their pathological mechanism is still unclear. Previous research has revealed that many forms of cell death, such as apoptosis and necrosis, occur in neurodegenerative diseases. Research in recent years has noticed that there is a new type of cell death in neurodegenerative diseases: ferroptosis. An increasing body of literature provides evidence for an involvement of ferroptosis in neurodegenerative diseases. SUMMARY In this article, we review a new form of cell death in neurodegenerative diseases: ferroptosis. Ferroptosis is defined as an iron-dependent form of regulated cell death, which occurs through the lethal accumulation of lipid-based reactive oxygen species when glutathione-dependent lipid peroxide repair systems are compromised. Several salient and established features of neurodegenerative diseases (including lipid peroxidation and iron dyshomeostasis) are consistent with ferroptosis, which means that ferroptosis may be involved in the progression of neurodegenerative diseases. In addition, as the center of energy metabolism in cells, mitochondria are also closely related to the regulation of iron homeostasis in the nervous system. At the same time, neurodegenerative diseases are often accompanied by degeneration of mitochondrial activity. Mitochondrial damage has been found to be involved in lipid peroxidation and iron dyshomeostasis in neurodegenerative diseases. Key Messages: Based on the summary of the related mechanisms of ferroptosis, we conclude that mitochondrial damage may affect neurodegenerative diseases by regulating many aspects of ferroptosis, including cell metabolism, iron dyshomeostasis, and lipid peroxidation.
-
3.
Siponimod (BAF312) Activates Nrf2 While Hampering NFκB in Human Astrocytes, and Protects From Astrocyte-Induced Neurodegeneration.
Colombo, E, Bassani, C, De Angelis, A, Ruffini, F, Ottoboni, L, Comi, G, Martino, G, Farina, C
Frontiers in immunology. 2020;:635
Abstract
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) with heterogeneous pathophysiology. In its progressive course oligodendrocyte and neuroaxonal damage is sustained by compartmentalized inflammation due to glial dysregulation. Siponimod (BAF312), a modulator of two sphingosine-1-phosphate (S1P) receptors (S1P1 and S1P5) is the first oral treatment specifically approved for active secondary progressive MS. To address potential direct effects of BAF312 on glial function and glia-neuron interaction, we set up a series of in vitro functional assays with astrocytes generated from human fibroblasts. These cells displayed the typical morphology and markers of astroglia, and were susceptible to the action of inflammatory mediators and BAF312, because expressing receptors for IL1, IL17, and S1P (namely S1P1 and S1P3). Targeting of S1P signaling by BAF312 inhibited NFκB translocation evoked by inflammatory cytokines, indicating a direct anti-inflammatory activity of the drug on the human astrocyte. Further, while glia cells exposed to IL1 or IL17 downregulated protein expression of glutamate transporters, BAF312-treated astrocytes maintained high levels of GLAST and GLT1 regardless of the presence of inflammatory mediators. Interestingly, despite potential glial susceptibility to S1P signaling via S1P3, which is not targeted by BAF312, NFκB translocation and downregulation of glutamate transporters in response to S1P were inhibited at similar levels by BAF312 and FTY720, another S1P signaling modulator targeting also S1P3. Accordingly, specific inhibition of S1P1 via NIBR-0213 blocked S1P-evoked NFκB translocation, demonstrating that modulation of S1P1 is sufficient to dampen signaling via other S1P receptors. Considering that NFκB-dependent responses are regulated by Nrf2, we measured activation of this critical transcription factor for anti-oxidant reactions, and observed that BAF312 rapidly induced nuclear translocation of Nrf2, but this effect was attenuated in the presence of an inflammatory milieu. Finally, in vitro experiments with spinal neurons exposed to astrocyte-conditioned media showed that modulation of S1P or cytokine signaling in astrocytes via BAF312 prevented neurons from astrocyte-induced degeneration. Overall, these experiments on human astrocytes suggest that during neuroinflammation targeting of S1P1 via BAF312 may modulate key astrocyte functions and thereby attain neuroprotection indirectly.
-
4.
Mitochondrial and redox dysfunction in post-menopause as risk factor of neurodegenerative disease: a pilot study testing the role of a validated Japanese functional food.
Marotta, F, Marcellino, M, Catanzaro, R, Campiotti, A, Lorenzetti, A, Cervi, J, Barbagallo, M
Journal of biological regulators and homeostatic agents. 2020;(1):111-121
Abstract
During the menopause women may experience increased oxidative stress and decreased antioxidant capacity and, together with the decline of neurosteroids, this represents a risk factor for Alzheimer's disease. The aim of the present study was to test a functional food (FPP-ORI, Osato Research Institute, Gifu, Japan) on redox and mitochondrial efficiency in post-menopausal women. The study population consisting of 69 untreated post-menopausal women were given supplements as follows: Group A was given a multivitamin (MV) 1c 2 times a day, and group B was given FPP 4.5 g 2 times a day. Group C consisted of 23 fertile premenopausal women as the control group. The tests carried out on entry, and at 3 and 6 months were erythrocyte redox parameters, plasma oxidated proteins, brain-derived neurotrophic factor (BDNF) and peripheral blood mononuclear cell (PBMC) mitochondria cytochrome c oxidase Vmax activity. Menopausal women showed an increased malondialdehyde (MDA) (p<0.05 vs control) which was normalized by both treatments (p<0.05), but MV failed to do so in the BMI ≥26 subgroup (p<0.05). All other redox enzymes and BDNF were significantly lower in menopausal women and they responded only to FPP (p<0.05). Carbonyl protein level was higher in "BMI ≥ 26" subgroup (p<0.05) and reduced only by FPP (p<0.05). The PBMC cyclooxygenase to citrate synthase activity was reduced (<40%) in the menopausal group (p<0.01) and only FPP caused a significant restoration (p<0.05). Although preliminary, these data confirm the redox and mitochondrial dysfunction occurring in post-menopause and responsive to FPP but very poorly to high dosage antioxidants. This may lead to potential preventive opportunities in menopause-associated neurodegenerative disease.
-
5.
Proteostasis Failure in Neurodegenerative Diseases: Focus on Oxidative Stress.
Höhn, A, Tramutola, A, Cascella, R
Oxidative medicine and cellular longevity. 2020;:5497046
Abstract
Protein homeostasis or proteostasis is an essential balance of cellular protein levels mediated through an extensive network of biochemical pathways that regulate different steps of the protein quality control, from the synthesis to the degradation. All proteins in a cell continuously turn over, contributing to development, differentiation, and aging. Due to the multiple interactions and connections of proteostasis pathways, exposure to stress conditions may cause various types of protein damage, altering cellular homeostasis and disrupting the entire network with additional cellular stress. Furthermore, protein misfolding and/or alterations during protein synthesis results in inactive or toxic proteins, which may overload the degradation mechanisms. The maintenance of a balanced proteome, preventing the formation of impaired proteins, is accomplished by two major catabolic routes: the ubiquitin proteasomal system (UPS) and the autophagy-lysosomal system. The proteostasis network is particularly important in nondividing, long-lived cells, such as neurons, as its failure is implicated with the development of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. These neurological disorders share common risk factors such as aging, oxidative stress, environmental stress, and protein dysfunction, all of which alter cellular proteostasis, suggesting that general mechanisms controlling proteostasis may underlay the etiology of these diseases. In this review, we describe the major pathways of cellular proteostasis and discuss how their disruption contributes to the onset and progression of neurodegenerative diseases, focusing on the role of oxidative stress.
-
6.
The Case for an Estrogen-iron Axis in Health and Disease.
Hamad, M, Bajbouj, K, Taneera, J
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2020;(4):270-277
Abstract
Clinical and experimental evidence suggest that estrogen manipulates intracellular iron metabolism and that elevated levels of estrogen associate with increased systemic iron availability. This has been attributed to the ability of estrogen to suppress hepcidin synthesis, maintain ferroportin integrity and enhance iron release from iron-absorbing duodenal enterocytes and iron-storing macrophages and hepatocytes. These observations speak of a potential "estrogen-iron" axis that manipulates iron metabolism in response to hematologic (erythropoiesis) and non-hematologic (uterine growth, pregnancy, lactation) needs for iron. Such an axis could contribute to minimizing iron deficiency in premenopausal women and iron overload in postmenopausal women. It could also exacerbate iron overload and related clinical consequences including cancer, osteoporosis, cardiovascular complications and neurodegenerative symptoms, especially in postmenopausal women on hormonal replacement therapy. Understanding the role of estrogen in iron metabolism may shed some light on the pleotropic, but often paradoxical, roles of estrogen in human health and disease.
-
7.
An Overview of Crucial Dietary Substances and Their Modes of Action for Prevention of Neurodegenerative Diseases.
Pogačnik, L, Ota, A, Ulrih, NP
Cells. 2020;(3)
Abstract
Neurodegenerative diseases, namely Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis are becoming one of the main health concerns due to the increasing aging of the world's population. These diseases often share the same biological mechanisms, including neuroinflammation, oxidative stress, and/or protein fibrillation. Recently, there have been many studies published pointing out the possibilities to reduce and postpone the clinical manifestation of these deadly diseases through lifelong consumption of some crucial dietary substances, among which phytochemicals (e.g., polyphenols) and endogenous substances (e.g., acetyl-L-carnitine, coenzyme Q10, n-3 poysaturated fatty acids) showed the most promising results. Another important issue that has been pointed out recently is the availability of these substances to the central nervous system, where they have to be present in high enough concentrations in order to exhibit their neuroprotective properties. As so, such the aim of this review is to summarize the recent findings regarding neuroprotective substances, their mechanisms of action, as well as to point out therapeutic considerations, including their bioavailability and safety for humans.
-
8.
A Review of Recent Patents (2016-2019) on Plant Food Supplements with Potential Application in the Treatment of Neurodegenerative and Metabolic Disorders.
Leuci, R, Brunetti, L, Laghezza, A, Tortorella, P, Loiodice, F, Piemontese, L
Recent patents on food, nutrition & agriculture. 2020;(2):145-153
Abstract
In the near future, it is expected that the prevalence of illnesses related to the increasing life expectancies and quality of life, such as neurodegenerative diseases and cardiovascular diseases related to metabolic disorders, will soar to unprecedented levels, leading to high socioeconomic costs. To address this rising threat, natural products are emerging as a novel strategy for the prevention and therapy of these ages- and lifestyle-related diseases, thanks to their high marketability and few side effects. In this patent review, we summarize selected patents for food supplements, functional and fortified foods, filed from 2016 to 2019, categorizing them based on the biological activity of their components.
-
9.
Rhinacanthus nasutus "Tea" Infusions and the Medicinal Benefits of the Constituent Phytochemicals.
Brimson, JM, Prasanth, MI, Malar, DS, Brimson, S, Tencomnao, T
Nutrients. 2020;(12)
Abstract
Rhinacanthus nasutus (L.) Kurz (Acanthaceae) (Rn) is an herbaceous shrub native to Thailand and much of South and Southeast Asia. It has several synonyms and local or common names. The root of Rn is used in Thai traditional medicine to treat snake bites, and the roots and/or leaves can be made into a balm and applied to the skin for the treatment of skin infections such as ringworm, or they may be brewed to form an infusion for the treatment of inflammatory disorders. Rn leaves are available to the public for purchase in the form of "tea bags" as a natural herbal remedy for a long list of disorders, including diabetes, skin diseases (antifungal, ringworm, eczema, scurf, herpes), gastritis, raised blood pressure, improved blood circulation, early-stage tuberculosis antitumor activity, and as an antipyretic. There have been many studies investigating the roles of Rn or compounds isolated from the herb regarding diseases such as Alzheimer's and other neurodegenerative diseases, cancer, diabetes and infection with bacteria, fungi or viruses. There have, however, been no clinical trials to confirm the efficacy of Rn in the treatment of any of these disorders, and the safety of these teas over long periods of consumption has never been tested. This review assesses the recent research into the role of Rn and its constituent compounds in a range of diseases.
-
10.
Adolescence and Aging: Impact of Adolescence Inflammatory Stress and Microbiota Alterations on Brain Development, Aging, and Neurodegeneration.
Yahfoufi, N, Matar, C, Ismail, N
The journals of gerontology. Series A, Biological sciences and medical sciences. 2020;(7):1251-1257
-
-
Free full text
-
Abstract
Puberty/adolescence is a critical phase during neurodevelopment with numerous structural, neurochemical, and molecular changes occurring in response to genetic and environmental signals. A consequence of this major neuronal reorganizing and remodeling is a heightened level of vulnerability to stressors and immune challenges. The gut microbiota is a fundamental modulator of stress and immune responses and has been found to play a role in mental health conditions and neurodegenerative disorders. Environmental insults (stress, infection, neuroinflammation, and use of antibiotics) during adolescence can result in dysbiosis subsidizing the development of brain disorders later in life. Also, pubertal neuroinflammatory insults can alter neurodevelopment, impact brain functioning in an enduring manner, and contribute to neurological disorders related to brain aging, such as Alzheimer's disease, Parkinson's disease, and depression. Exposure to probiotics during puberty can mitigate inflammation, reverse dysbiosis, and decrease vulnerabilities to brain disorders later in life. The goal of this review is to reveal the consequences of pubertal exposure to stress and immune challenges on the gut microbiota, immune reactivity within the brain, and the risk or resilience to stress-induced mental illnesses and neurodegenerative disorders. We propose that the consumption of probiotics during adolescence contribute to the prevention of brain pathologies in adulthood.