GDNF and protection of adult central catecholaminergic neurons

Neurotrophic factors are small proteins necessary for neuron survival and maintenance of phenotype. They are considered as promising therapeutic tools for neurodegenerative diseases. The glial cell line-derived neurotrophic factor (GDNF) protects catecholaminergic cells from toxic insults; thus, its potential therapeutic applicability in Parkinson's disease has been intensely investigated. In recent years, there have been major advances in the analysis of GDNF signaling pathways in peripheral neurons and embryonic dopamine mesencephalic cells. However, the actual physiological role of GDNF in maintaining catecholaminergic central neurons during adulthood is only starting to be unraveled, and the mechanisms whereby GDNF protects central brain neurons are poorly known. In this study, we review the current knowledge of GDNF expression, signaling, and function in adult brain, with special emphasis on the genetic animal models with deficiency in the GDNF-dependent pathways.

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Estrogen and Spermatogenesis*

Endocrine Reviews ◽

10.1210/edrv.22.3.0431 ◽

2001 ◽

Vol 22 (3) ◽

pp. 289-318 ◽

Cited By ~ 119

Author(s):

Liza O’Donnell ◽

Kirsten M. Robertson ◽

Margaret E. Jones ◽

Evan R. Simpson

Keyword(s):

Estrogen Receptors ◽

Male Fertility ◽

Current Knowledge ◽

Physiological Role ◽

Local Context ◽

Normal Male ◽

Estrogen Exposure ◽

And Function ◽

Estrogen Administration

Abstract Although it has been known for many years that estrogen administration has deleterious effects on male fertility, data from transgenic mice deficient in estrogen receptors or aromatase point to an essential physiological role for estrogen in male fertility. This review summarizes the current knowledge on the localization of estrogen receptors and aromatase in the testis in an effort to understand the likely sites of estrogen action. The review also discusses the many studies that have used models employing the administration of estrogenic substances to show that male fertility is responsive to estrogen, thus providing a mechanism by which inappropriate exposure to estrogenic substances may cause adverse effects on spermatogenesis and male fertility. The reproductive phenotypes of mice deficient in estrogen receptors α and/or β and aromatase are also compared to evaluate the physiological role of estrogen in male fertility. The review focuses on the effects of estrogen administration or deprivation, primarily in rodents, on the hypothalamo-pituitary-testis axis, testicular function (including Leydig cell, Sertoli cell, and germ cell development and function), and in the development and function of the efferent ductules and epididymis. The requirement for estrogen in normal male sexual behavior is also reviewed, along with the somewhat limited data on the fertility of men who lack either the capacity to produce or respond to estrogen. This review highlights the ability of exogenous estrogen exposure to perturb spermatogenesis and male fertility, as well as the emerging physiological role of estrogens in male fertility, suggesting that, in this local context, estrogenic substances should also be considered “male hormones.”

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The Oxford Handbook of the Auditory Brainstem

10.1093/oxfordhb/9780190849061.001.0001 ◽

2018 ◽

Cited By ~ 1

Keyword(s):

Current Knowledge ◽

Auditory Pathway ◽

Auditory Brainstem ◽

Auditory Midbrain ◽

Current State ◽

Neuronal Mechanisms ◽

Maladaptive Plasticity ◽

And Function ◽

Auditory Field

The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.

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Sialic Acid—Modified Nanoparticles—New Approaches in the Glioma Management—Perspective Review

International Journal of Molecular Sciences ◽

10.3390/ijms22147494 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7494

Author(s):

Przemyslaw Wielgat ◽

Katarzyna Niemirowicz-Laskowska ◽

Agnieszka Z. Wilczewska ◽

Halina Car

Keyword(s):

Sialic Acid ◽

Clinical Observation ◽

Malignant Cell ◽

Cellular Heterogeneity ◽

Molecular Processes ◽

Management Perspective ◽

Therapeutic Tools ◽

And Function ◽

Worse Prognosis

The cell surface is covered by a dense and complex network of glycans attached to the membrane proteins and lipids. In gliomas, the aberrant sialylation, as the final stage of glycosylation, is an important regulatory mechanism of malignant cell behavior and correlates with worse prognosis. Better understanding of the role of sialylation in cellular and molecular processes opens a new way in the development of therapeutic tools for human brain tumors. According to the recent clinical observation, the cellular heterogeneity, activity of brain cancer stem cells (BCSCs), immune evasion, and function of the blood–brain barrier (BBB) are attractive targets for new therapeutic strategies. In this review, we summarize the importance of sialic acid-modified nanoparticles in brain tumor progression.

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Antioxidant and Signaling Role of Plastid-Derived Isoprenoid Quinones and Chromanols

International Journal of Molecular Sciences ◽

10.3390/ijms22062950 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2950

Author(s):

Beatrycze Nowicka ◽

Agnieszka Trela-Makowej ◽

Dariusz Latowski ◽

Kazimierz Strzalka ◽

Renata Szymańska

Keyword(s):

Current Knowledge ◽

Stress Factors ◽

Oxygenic Photosynthesis ◽

Ros Generation ◽

Main Site ◽

Storage Lipids ◽

Abiotic Stress Factors ◽

Cell Components ◽

And Function

Plant prenyllipids, especially isoprenoid chromanols and quinols, are very efficient low-molecular-weight lipophilic antioxidants, protecting membranes and storage lipids from reactive oxygen species (ROS). ROS are byproducts of aerobic metabolism that can damage cell components, they are also known to play a role in signaling. Plants are particularly prone to oxidative damage because oxygenic photosynthesis results in O2 formation in their green tissues. In addition, the photosynthetic electron transfer chain is an important source of ROS. Therefore, chloroplasts are the main site of ROS generation in plant cells during the light reactions of photosynthesis, and plastidic antioxidants are crucial to prevent oxidative stress, which occurs when plants are exposed to various types of stress factors, both biotic and abiotic. The increase in antioxidant content during stress acclimation is a common phenomenon. In the present review, we describe the mechanisms of ROS (singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radical) production in chloroplasts in general and during exposure to abiotic stress factors, such as high light, low temperature, drought and salinity. We highlight the dual role of their presence: negative (i.e., lipid peroxidation, pigment and protein oxidation) and positive (i.e., contribution in redox-based physiological processes). Then we provide a summary of current knowledge concerning plastidic prenyllipid antioxidants belonging to isoprenoid chromanols and quinols, as well as their structure, occurrence, biosynthesis and function both in ROS detoxification and signaling.

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Non-Coding RNA in Pancreas and β-Cell Development

Non-Coding RNA ◽

10.3390/ncrna4040041 ◽

2018 ◽

Vol 4 (4) ◽

pp. 41 ◽

Cited By ~ 7

Author(s):

Wilson K. M. Wong ◽

Anja E. Sørensen ◽

Mugdha V. Joglekar ◽

Anand A. Hardikar ◽

Louise T. Dalgaard

Keyword(s):

Cell Function ◽

Islet Cells ◽

Current Knowledge ◽

Cell Development ◽

Pancreas Development ◽

Β Cell ◽

Neighboring Gene ◽

Non Coding Rnas ◽

And Function

In this review, we provide an overview of the current knowledge on the role of different classes of non-coding RNAs for islet and β-cell development, maturation and function. MicroRNAs (miRNAs), a prominent class of small RNAs, have been investigated for more than two decades and patterns of the roles of different miRNAs in pancreatic fetal development, islet and β-cell maturation and function are now emerging. Specific miRNAs are dynamically regulated throughout the period of pancreas development, during islet and β-cell differentiation as well as in the perinatal period, where a burst of β-cell replication takes place. The role of long non-coding RNAs (lncRNA) in islet and β-cells is less investigated than for miRNAs, but knowledge is increasing rapidly. The advent of ultra-deep RNA sequencing has enabled the identification of highly islet- or β-cell-selective lncRNA transcripts expressed at low levels. Their roles in islet cells are currently only characterized for a few of these lncRNAs, and these are often associated with β-cell super-enhancers and regulate neighboring gene activity. Moreover, ncRNAs present in imprinted regions are involved in pancreas development and β-cell function. Altogether, these observations support significant and important actions of ncRNAs in β-cell development and function.

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T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells

Frontiers in Immunology ◽

10.3389/fimmu.2021.732511 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laura Kiekens ◽

Wouter Van Loocke ◽

Sylvie Taveirne ◽

Sigrid Wahlen ◽

Eva Persyn ◽

...

Keyword(s):

Nk Cells ◽

Natural Killer ◽

Cell Biology ◽

Nk Cell ◽

Current Knowledge ◽

Functional Differentiation ◽

Cell Maturation ◽

Hematopoietic Stem ◽

And Function

T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.

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Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver

Cells ◽

10.3390/cells11020288 ◽

2022 ◽

Vol 11 (2) ◽

pp. 288

Author(s):

Julie Massart ◽

Karima Begriche ◽

Jessica H. Hartman ◽

Bernard Fromenty

Keyword(s):

Oxidative Stress ◽

Cytochrome P450 ◽

Liver Disease ◽

Fatty Liver ◽

Current Knowledge ◽

Physiological Role ◽

Experimental Investigations ◽

Rat Liver Mitochondria ◽

Cytochrome P450 2E1

Cytochrome P450 2E1 (CYP2E1) is pivotal in hepatotoxicity induced by alcohol abuse and different xenobiotics. In this setting, CYP2E1 generates reactive metabolites inducing oxidative stress, mitochondrial dysfunction and cell death. In addition, this enzyme appears to play a role in the progression of obesity-related fatty liver to nonalcoholic steatohepatitis. Indeed, increased CYP2E1 activity in nonalcoholic fatty liver disease (NAFLD) is deemed to induce reactive oxygen species overproduction, which in turn triggers oxidative stress, necroinflammation and fibrosis. In 1997, Avadhani’s group reported for the first time the presence of CYP2E1 in rat liver mitochondria, and subsequent investigations by other groups confirmed that mitochondrial CYP2E1 (mtCYP2E1) could be found in different experimental models. In this review, we first recall the main features of CYP2E1 including its role in the biotransformation of endogenous and exogenous molecules, the regulation of its expression and activity and its involvement in different liver diseases. Then, we present the current knowledge on the physiological role of mtCYP2E1, its contribution to xenobiotic biotransformation as well as the mechanism and regulation of CYP2E1 targeting to mitochondria. Finally, we discuss experimental investigations suggesting that mtCYP2E1 could have a role in alcohol-associated liver disease, xenobiotic-induced hepatotoxicity and NAFLD.

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Retromer subunit, VPS29, regulates synaptic transmission and is required for endolysosomal function in the aging brain

eLife ◽

10.7554/elife.51977 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 4

Author(s):

Hui Ye ◽

Shamsideen A Ojelade ◽

David Li-Kroeger ◽

Zhongyuan Zuo ◽

Liping Wang ◽

...

Keyword(s):

Synaptic Transmission ◽

Protein Complex ◽

Adult Brain ◽

Aging Brain ◽

Gtpase Activating Protein ◽

Ultrastructural Evidence ◽

Aging Adults ◽

And Function ◽

Brain Homeostasis

Retromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. Although implicated in both Parkinson’s and Alzheimer’s disease, our understanding of retromer function in the adult brain remains limited, in part because Vps35 and Vps26 are essential for development. In Drosophila, we find that Vps29 is dispensable for embryogenesis but required for retromer function in aging adults, including for synaptic transmission, survival, and locomotion. Unexpectedly, in Vps29 mutants, Vps35 and Vps26 proteins are normally expressed and associated, but retromer is mislocalized from neuropil to soma with the Rab7 GTPase. Further, Vps29 phenotypes are suppressed by reducing Rab7 or overexpressing the GTPase activating protein, TBC1D5. With aging, retromer insufficiency triggers progressive endolysosomal dysfunction, with ultrastructural evidence of impaired substrate clearance and lysosomal stress. Our results reveal the role of Vps29 in retromer localization and function, highlighting requirements for brain homeostasis in aging.

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