International Journal of Molecular Sciences

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21 pages, 567 KiB

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Neurodegeneration and Neuro-Regeneration—Alzheimer’s Disease and Stem Cell Therapy

by Verica Vasic, Kathrin Barth and Mirko H.H. Schmidt

Int. J. Mol. Sci. 2019, 20(17), 4272; https://doi.org/10.3390/ijms20174272 - 31 Aug 2019

Cited by 86 | Viewed by 13594

Aging causes many changes in the human body, and is a high risk for various diseases. Dementia, a common age-related disease, is a clinical disorder triggered by neurodegeneration. Brain damage caused by neuronal death leads to cognitive decline, memory loss, learning inabilities and [...] Read more.

Aging causes many changes in the human body, and is a high risk for various diseases. Dementia, a common age-related disease, is a clinical disorder triggered by neurodegeneration. Brain damage caused by neuronal death leads to cognitive decline, memory loss, learning inabilities and mood changes. Numerous disease conditions may cause dementia; however, the most common one is Alzheimer’s disease (AD), a futile and yet untreatable illness. Adult neurogenesis carries the potential of brain self-repair by an endogenous formation of newly-born neurons in the adult brain; however it also declines with age. Strategies to improve the symptoms of aging and age-related diseases have included different means to stimulate neurogenesis, both pharmacologically and naturally. Finally, the regulatory mechanisms of stem cells neurogenesis or a functional integration of newborn neurons have been explored to provide the basis for grafted stem cell therapy. This review aims to provide an overview of AD pathology of different neural and glial cell types and summarizes current strategies of experimental stem cell treatments and their putative future use in clinical settings. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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32 pages, 1082 KiB

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Molecular Mechanisms of Cancer-Induced Sleep Disruption

by William H. Walker II and Jeremy C. Borniger

Int. J. Mol. Sci. 2019, 20(11), 2780; https://doi.org/10.3390/ijms20112780 - 6 Jun 2019

Cited by 79 | Viewed by 10375

Abstract

Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting the role of sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients [...] Read more.

Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting the role of sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifesting as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in the patients’ quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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17 pages, 1294 KiB

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Crazy Little Thing Called Sox—New Insights in Oligodendroglial Sox Protein Function

by Jan Wittstatt, Simone Reiprich and Melanie Küspert

Int. J. Mol. Sci. 2019, 20(11), 2713; https://doi.org/10.3390/ijms20112713 - 2 Jun 2019

Cited by 14 | Viewed by 5299

Abstract

In the central nervous system, oligodendrocytes wrap axons with myelin sheaths, which is essential for rapid transfer of electric signals and their trophic support. In oligodendroglia, transcription factors of the Sox protein family are pivotal regulators of a variety of developmental processes. These [...] Read more.

In the central nervous system, oligodendrocytes wrap axons with myelin sheaths, which is essential for rapid transfer of electric signals and their trophic support. In oligodendroglia, transcription factors of the Sox protein family are pivotal regulators of a variety of developmental processes. These include specification, proliferation, and migration of oligodendrocyte precursor cells as well as terminal differentiation to mature myelinating oligodendrocytes. Sox proteins are further affected in demyelinating diseases and are involved in remyelination following damage of the central nervous system. Here we summarize and discuss latest findings on transcriptional regulation of Sox proteins, their function, target genes, and interaction with other transcription factors and chromatin remodelers in oligodendroglia with physiological and pathophysiological relevance. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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14 pages, 5112 KiB

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Structural Insights into the Molecular Evolution of the Archaeal Exo-β-d-Glucosaminidase

by Shouhei Mine and Masahiro Watanabe

Int. J. Mol. Sci. 2019, 20(10), 2460; https://doi.org/10.3390/ijms20102460 - 18 May 2019

Cited by 3 | Viewed by 3026

Abstract

The archaeal exo-β-d-glucosaminidase (GlmA), a thermostable enzyme belonging to the glycosidase hydrolase (GH) 35 family, hydrolyzes chitosan oligosaccharides into monomer glucosamines. GlmA is a novel enzyme in terms of its primary structure, as it is homologous to both GH35 and GH42 [...] Read more.

The archaeal exo-β-d-glucosaminidase (GlmA), a thermostable enzyme belonging to the glycosidase hydrolase (GH) 35 family, hydrolyzes chitosan oligosaccharides into monomer glucosamines. GlmA is a novel enzyme in terms of its primary structure, as it is homologous to both GH35 and GH42 β-galactosidases. The catalytic mechanism of GlmA is not known. Here, we summarize the recent reports on the crystallographic analysis of GlmA. GlmA is a homodimer, with each subunit comprising three distinct domains: a catalytic TIM-barrel domain, an α/β domain, and a β1 domain. Surprisingly, the structure of GlmA presents features common to GH35 and GH42 β-galactosidases, with the domain organization resembling that of GH42 β-galactosidases and the active-site architecture resembling that of GH35 β-galactosidases. Additionally, the GlmA structure also provides critical information about its catalytic mechanism, in particular, on how the enzyme can recognize glucosamine. Finally, we postulate an evolutionary pathway based on the structure of an ancestor GlmA to extant GH35 and GH42 β-galactosidases. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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20 pages, 1463 KiB

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Methods for the Refinement of Protein Structure 3D Models

by Recep Adiyaman and Liam James McGuffin

Int. J. Mol. Sci. 2019, 20(9), 2301; https://doi.org/10.3390/ijms20092301 - 9 May 2019

Cited by 43 | Viewed by 7289

Abstract

The refinement of predicted 3D protein models is crucial in bringing them closer towards experimental accuracy for further computational studies. Refinement approaches can be divided into two main stages: The sampling and scoring stages. Sampling strategies, such as the popular Molecular Dynamics (MD)-based [...] Read more.

The refinement of predicted 3D protein models is crucial in bringing them closer towards experimental accuracy for further computational studies. Refinement approaches can be divided into two main stages: The sampling and scoring stages. Sampling strategies, such as the popular Molecular Dynamics (MD)-based protocols, aim to generate improved 3D models. However, generating 3D models that are closer to the native structure than the initial model remains challenging, as structural deviations from the native basin can be encountered due to force-field inaccuracies. Therefore, different restraint strategies have been applied in order to avoid deviations away from the native structure. For example, the accurate prediction of local errors and/or contacts in the initial models can be used to guide restraints. MD-based protocols, using physics-based force fields and smart restraints, have made significant progress towards a more consistent refinement of 3D models. The scoring stage, including energy functions and Model Quality Assessment Programs (MQAPs) are also used to discriminate near-native conformations from non-native conformations. Nevertheless, there are often very small differences among generated 3D models in refinement pipelines, which makes model discrimination and selection problematic. For this reason, the identification of the most native-like conformations remains a major challenge. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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15 pages, 1487 KiB

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Neutrophil Cell Shape Change: Mechanism and Signalling during Cell Spreading and Phagocytosis

by Rhiannon E. Roberts and Maurice B. Hallett

Int. J. Mol. Sci. 2019, 20(6), 1383; https://doi.org/10.3390/ijms20061383 - 19 Mar 2019

Cited by 47 | Viewed by 8259

Abstract

Perhaps the most important feature of neutrophils is their ability to rapidly change shape. In the bloodstream, the neutrophils circulate as almost spherical cells, with the ability to deform in order to pass along narrower capillaries. Upon receiving the signal to extravasate, they [...] Read more.

Perhaps the most important feature of neutrophils is their ability to rapidly change shape. In the bloodstream, the neutrophils circulate as almost spherical cells, with the ability to deform in order to pass along narrower capillaries. Upon receiving the signal to extravasate, they are able to transform their morphology and flatten onto the endothelium surface. This transition, from a spherical to a flattened morphology, is the first key step which neutrophils undergo before moving out of the blood and into the extravascular tissue space. Once they have migrated through tissues towards sites of infection, neutrophils carry out their primary role—killing infecting microbes by performing phagocytosis and producing toxic reactive oxygen species within the microbe-containing phagosome. Phagocytosis involves the second key morphology change that neutrophils undergo, with the formation of pseudopodia which capture the microbe within an internal vesicle. Both the spherical to flattened stage and the phagocytic capture stage are rapid, each being completed within 100 s. Knowing how these rapid cell shape changes occur in neutrophils is thus fundamental to understanding neutrophil behaviour. This article will discuss advances in our current knowledge of this process, and also identify an important regulated molecular event which may represent an important target for anti-inflammatory therapy. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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13 pages, 913 KiB

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Pharmacological Utilization of Bergamottin, Derived from Grapefruits, in Cancer Prevention and Therapy

by Jeong-Hyeon Ko, Frank Arfuso, Gautam Sethi and Kwang Seok Ahn

Int. J. Mol. Sci. 2018, 19(12), 4048; https://doi.org/10.3390/ijms19124048 - 14 Dec 2018

Cited by 38 | Viewed by 6917

Abstract

Cancer still remains one of the leading causes of death worldwide. In spite of significant advances in treatment options and the advent of novel targeted therapies, there still remains an unmet need for the identification of novel pharmacological agents for cancer therapy. This [...] Read more.

Cancer still remains one of the leading causes of death worldwide. In spite of significant advances in treatment options and the advent of novel targeted therapies, there still remains an unmet need for the identification of novel pharmacological agents for cancer therapy. This has led to several studies evaluating the possible application of natural agents found in vegetables, fruits, or plant-derived products that may be useful for cancer treatment. Bergamottin is a furanocoumarin derived from grapefruits and is also a well-known cytochrome P450 inhibitor. Recent studies have demonstrated potent anti-oxidative, anti-inflammatory, and anti-cancer properties of grapefruit furanocoumarin both in vitro and in vivo. The present review focuses on the potential anti-neoplastic effects of bergamottin in different tumor models and briefly describes the molecular targets affected by this agent. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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19 pages, 977 KiB

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TIPE Family of Proteins and Its Implications in Different Chronic Diseases

by Devivasha Bordoloi, Kishore Banik, Bano Shabnam, Ganesan Padmavathi, Javadi Monisha, Frank Arfuso, Arunasalam Dharmarajan, Xinliang Mao, Lina H. K. Lim, Lingzhi Wang, Lu Fan, Kam Man Hui, Alan Prem Kumar, Gautam Sethi and Ajaikumar B. Kunnumakkara

Int. J. Mol. Sci. 2018, 19(10), 2974; https://doi.org/10.3390/ijms19102974 - 29 Sep 2018

Cited by 62 | Viewed by 6739

Abstract

The tumor necrosis factor-α-induced protein 8-like (TIPE/TNFAIP8) family is a recently identified family of proteins that is strongly associated with the regulation of immunity and tumorigenesis. This family is comprised of four members, namely, tumor necrosis factor-α-induced protein 8 (TIPE/TNFAIP8), tumor necrosis factor-α-induced [...] Read more.

The tumor necrosis factor-α-induced protein 8-like (TIPE/TNFAIP8) family is a recently identified family of proteins that is strongly associated with the regulation of immunity and tumorigenesis. This family is comprised of four members, namely, tumor necrosis factor-α-induced protein 8 (TIPE/TNFAIP8), tumor necrosis factor-α-induced protein 8-like 1 (TIPE1/TNFAIP8L1), tumor necrosis factor-α-induced protein 8-like 2 (TIPE2/TNFAIP8L2), and tumor necrosis factor-α-induced protein 8-like 3 (TIPE3/TNFAIP8L3). Although the proteins of this family were initially described as regulators of tumorigenesis, inflammation, and cell death, they are also found to be involved in the regulation of autophagy and the transfer of lipid secondary messengers, besides contributing to immune function and homeostasis. Interestingly, despite the existence of a significant sequence homology among the four members of this family, they are involved in different biological activities and also exhibit remarkable variability of expression. Furthermore, this family of proteins is highly deregulated in different human cancers and various chronic diseases. This review summarizes the vivid role of the TIPE family of proteins and its association with various signaling cascades in diverse chronic diseases. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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49 pages, 627 KiB

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Aloe Genus Plants: From Farm to Food Applications and Phytopharmacotherapy

by Bahare Salehi, Sevil Albayrak, Hubert Antolak, Dorota Kręgiel, Ewelina Pawlikowska, Mehdi Sharifi-Rad, Yadav Uprety, Patrick Valere Tsouh Fokou, Zubaida Yousef, Zainul Amiruddin Zakaria, Elena Maria Varoni, Farukh Sharopov, Natália Martins, Marcello Iriti and Javad Sharifi-Rad

Int. J. Mol. Sci. 2018, 19(9), 2843; https://doi.org/10.3390/ijms19092843 - 19 Sep 2018

Cited by 128 | Viewed by 19255

Abstract

Aloe genus plants, distributed in Old World, are widely known and have been used for centuries as topical and oral therapeutic agents due to their health, beauty, medicinal, and skin care properties. Among the well-investigated Aloe species are A. arborescens, A. barbadensis [...] Read more.

Aloe genus plants, distributed in Old World, are widely known and have been used for centuries as topical and oral therapeutic agents due to their health, beauty, medicinal, and skin care properties. Among the well-investigated Aloe species are A. arborescens, A. barbadensis, A. ferox, and A. vera. Today, they account among the most economically important medicinal plants and are commonly used in primary health treatment, where they play a pivotal role in the treatment of various types of diseases via the modulation of biochemical and molecular pathways, besides being a rich source of valuable phytochemicals. In the present review, we summarized the recent advances in botany, phytochemical composition, ethnobotanical uses, food preservation, and the preclinical and clinical efficacy of Aloe plants. These data will be helpful to provide future directions for the industrial and medicinal use of Aloe plants. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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42 pages, 1095 KiB

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The Sugar-Signaling Hub: Overview of Regulators and Interaction with the Hormonal and Metabolic Network

by Soulaiman Sakr, Ming Wang, Fabienne Dédaldéchamp, Maria-Dolores Perez-Garcia, Laurent Ogé, Latifa Hamama and Rossitza Atanassova

Int. J. Mol. Sci. 2018, 19(9), 2506; https://doi.org/10.3390/ijms19092506 - 24 Aug 2018

Cited by 163 | Viewed by 12652

Abstract

Plant growth and development has to be continuously adjusted to the available resources. Their optimization requires the integration of signals conveying the plant metabolic status, its hormonal balance, and its developmental stage. Many investigations have recently been conducted to provide insights into sugar [...] Read more.

Plant growth and development has to be continuously adjusted to the available resources. Their optimization requires the integration of signals conveying the plant metabolic status, its hormonal balance, and its developmental stage. Many investigations have recently been conducted to provide insights into sugar signaling and its interplay with hormones and nitrogen in the fine-tuning of plant growth, development, and survival. The present review emphasizes the diversity of sugar signaling integrators, the main molecular and biochemical mechanisms related to the sugar-signaling dependent regulations, and to the regulatory hubs acting in the interplay of the sugar-hormone and sugar-nitrogen networks. It also contributes to compiling evidence likely to fill a few knowledge gaps, and raises new questions for the future. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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12 pages, 782 KiB

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N6-Methyladenosine Role in Acute Myeloid Leukaemia

by Zaira Ianniello and Alessandro Fatica

Int. J. Mol. Sci. 2018, 19(8), 2345; https://doi.org/10.3390/ijms19082345 - 9 Aug 2018

Cited by 39 | Viewed by 5678

Abstract

We are currently assisting in the explosion of epitranscriptomics, which studies the functional role of chemical modifications into RNA molecules. Among more than 100 RNA modifications, the N6-methyladenosine (m⁶A), in particular, has attracted the interest of researchers all around the world. [...] Read more.

We are currently assisting in the explosion of epitranscriptomics, which studies the functional role of chemical modifications into RNA molecules. Among more than 100 RNA modifications, the N6-methyladenosine (m⁶A), in particular, has attracted the interest of researchers all around the world. m⁶A is the most abundant internal chemical modification in mRNA, and it can control any aspect of mRNA post-transcriptional regulation. m⁶A is installed by “writers”, removed by “erasers”, and recognized by “readers”; thus, it can be compared to the reversible and dynamic epigenetic modifications in histones and DNA. Given its fundamental role in determining the way mRNAs are expressed, it comes as no surprise that alterations to m⁶A modifications have a deep impact in cell differentiation, normal development and human diseases. Here, we review the proteins involved in m⁶A modification in mammals, m⁶A role in gene expression and its contribution to cancer development. In particular, we will focus on acute myeloid leukaemia (AML), which provides an initial indication of how alteration in m⁶A modification can disrupt normal cellular differentiation and lead to cancer. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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21 pages, 787 KiB

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Phenolic Compounds Isolated from Olive Oil as Nutraceutical Tools for the Prevention and Management of Cancer and Cardiovascular Diseases

by Patricia Reboredo-Rodríguez, Alfonso Varela-López, Tamara Y. Forbes-Hernández, Massimiliano Gasparrini, Sadia Afrin, Danila Cianciosi, Jiaojiao Zhang, Piera Pia Manna, Stefano Bompadre, José L. Quiles, Maurizio Battino and Francesca Giampieri

Int. J. Mol. Sci. 2018, 19(8), 2305; https://doi.org/10.3390/ijms19082305 - 6 Aug 2018

Cited by 94 | Viewed by 8582

Abstract

Non-communicable diseases (NCDs) have become the largest contributor to worldwide morbidity and mortality. Among them, cancer and cardiovascular diseases (CVDs) are responsible for a 47% of worldwide mortality. In general, preventive approaches modifying lifestyle are more cost-effective than treatments after disease onset. In [...] Read more.

Non-communicable diseases (NCDs) have become the largest contributor to worldwide morbidity and mortality. Among them, cancer and cardiovascular diseases (CVDs) are responsible for a 47% of worldwide mortality. In general, preventive approaches modifying lifestyle are more cost-effective than treatments after disease onset. In this sense, a healthy diet could help a range of NCDs, such as cancer and CVDs. Traditional Mediterranean Diet (MD) is associated by the low-prevalence of certain types of cancers and CVDs, where olive oil plays an important role. In fact, different epidemiological studies suggest that olive oil consumption prevents some cancers, as well as coronary heart diseases and stroke incidence and mortality. Historically, the beneficial health effects of virgin olive oil (VOO) intake were first attributed to the high concentration of monounsaturated fatty acids. Nowadays, many studies indicate that phenolic compounds contained in olive oil have positive effects on different biomarkers related to health. Among them, phenolic compounds would be partially responsible for health benefits. The present work aims to explore, in studies published during the last five years, the effects of the main phenolic compounds isolated from olive oil on different cancer or CVD aspects, in order to clarify which compounds have more potential to be used as nutraceuticals with preventive or even therapeutic properties. Full article

(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)

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