scholarly journals MAPK/ERK Dysfunction in Neurodegenerative Diseases

2020 ◽  
Author(s):  
Hector Albert Gasco ◽  
FRANCISCO ROS-BERNAL ◽  
ESTHER CASTILLO-GÓMEZ ◽  
Francisco Olucha-Bordonau
Keyword(s):  
Neurodegenerative Diseases ◽  
Expression Patterns ◽  
Common Mechanism ◽  
Neural Structure ◽  
Cellular Element ◽  
Intracellular Space ◽  
Stage Of Development ◽  
Extracellular Stimuli ◽  
The Central Nervous System ◽  
Extracellular Regulated Kinase

The signaling pathway of the microtubule-associated protein kinase or extracellular regulated kinase (MAPK/ERK) is a common mechanism of extracellular information transduction from extracellular stimuli to the intracellular space. The transduction of information leads to changes in the ongoing metabolic pathways and the modification of gene expression patterns. In the central nervous system, ERK is expressed ubiquitously, both temporally and spatially. The MAP-ERK pathway is a key element of the neuroinflammatory pathway triggered by glial cells during the development of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, as well as prionic diseases. The process triggered by MAPK/ERK activation depends on the stage of development (mature or senescence), the type of cellular element in which the pathway is activated, and the anatomic neural structure. However, extensive gaps exist with regards to the targets of the phosphorylated ERK in many of these processes.

scholarly journals MAP/ERK Signaling in Developing Cognitive and Emotional Function and Its Effect on Pathological and Neurodegenerative Processes

2020 ◽  
Vol 21 (12) ◽  
pp. 4471 ◽  
Author(s):  
Héctor Albert-Gascó ◽  
Francisco Ros-Bernal ◽  
Esther Castillo-Gómez ◽  
Francisco E. Olucha-Bordonau
Keyword(s):  
Embryonic Development ◽  
Genetic Alterations ◽  
Autism Spectrum ◽  
Postnatal Period ◽  
Emotional Behavior ◽  
Early Postnatal Period ◽  
Common Mechanism ◽  
Erk Pathway ◽  
Intracellular Space ◽  
Stage Of Development

The signaling pathway of the microtubule-associated protein kinase or extracellular regulated kinase (MAPK/ERK) is a common mechanism of extracellular information transduction from extracellular stimuli to the intracellular space. The transduction of information leads to changes in the ongoing metabolic pathways and the modification of gene expression patterns. In the central nervous system, ERK is expressed ubiquitously, both temporally and spatially. As for the temporal ubiquity, this signaling system participates in three key moments: (i) Embryonic development; (ii) the early postnatal period; and iii) adulthood. During embryonic development, the system is partly responsible for the patterning of segmentation in the encephalic vesicle through the FGF8-ERK pathway. In addition, during this period, ERK directs neurogenesis migration and the final fate of neural progenitors. During the early postnatal period, ERK participates in the maturation process of dendritic trees and synaptogenesis. During adulthood, ERK participates in social and emotional behavior and memory processes, including long-term potentiation. Alterations in mechanisms related to ERK are associated with different pathological outcomes. Genetic alterations in any component of the ERK pathway result in pathologies associated with neural crest derivatives and mental dysfunctions associated with autism spectrum disorders. The MAP-ERK pathway is a key element of the neuroinflammatory pathway triggered by glial cells during the development of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, as well as prionic diseases. The process triggered by MAPK/ERK activation depends on the stage of development (mature or senescence), the type of cellular element in which the pathway is activated, and the anatomic neural structure. However, extensive gaps exist with regards to the targets of the phosphorylated ERK in many of these processes.

scholarly journals Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions

2021 ◽  
Vol 15 ◽  
Author(s):  
Junko Nio-Kobayashi ◽  
Tetsuya Itabashi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Glial Cells ◽  
Expression Patterns ◽  
Neural Regeneration ◽  
Oligodendrocyte Differentiation ◽  
Cellular Expression ◽  
Galectin 3 ◽  
The Central Nervous System

Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system (CNS) and regulate various physiological and pathological events. This review summarizes the current knowledge of the cellular expression and role of galectins in the CNS, and discusses their functions in neurite outgrowth, myelination, and neural stem/progenitor cell niches, as well as in ischemic/hypoxic/traumatic injuries and neurodegenerative diseases such as multiple sclerosis. Galectins are expressed in both neurons and glial cells. Galectin-1 is mainly expressed in motoneurons, whereas galectin-3-positive neurons are broadly distributed throughout the brain, especially in the hypothalamus, indicating its function in the regulation of homeostasis, stress response, and the endocrine/autonomic system. Astrocytes predominantly contain galectin-1, and galectin-3 and−9 are upregulated along with its activation. Activated, but not resting, microglia contain galectin-3, supporting its phagocytic activity. Galectin-1,−3, and -4 are characteristically expressed during oligodendrocyte differentiation. Galectin-3 from microglia promotes oligodendrocyte differentiation and myelination, while galectin-1 and axonal galectin-4 suppress its differentiation and myelination. Galectin-1- and- 3-positive cells are involved in neural stem cell niche formation in the subventricular zone and hippocampal dentate gyrus, and the migration of newly generated neurons and glial cells to the olfactory bulb or damaged lesions. In neurodegenerative diseases, galectin-1,-8, and -9 have neuroprotective and anti-inflammatory activities. Galectin-3 facilitates pro-inflammatory action; however, it also plays an important role during the recovery period. Several ligand glycoconjugates have been identified so far such as laminin, integrins, neural cell adhesion molecule L1, sulfatide, neuropilin-1/plexinA4 receptor complex, triggering receptor on myeloid cells 2, and T cell immunoglobulin and mucin domain. N-glycan branching on lymphocytes and oligodendroglial progenitors mediated by β1,6-N-acetylglucosaminyltransferase V (Mgat5/GnTV) influences galectin-binding, modulating inflammatory responses and remyelination in neurodegenerative diseases. De-sulfated galactosaminoglycans such as keratan sulfate are potential ligands for galectins, especially galectin-3, regulating neural regeneration. Galectins have multitudinous functions depending on cell type and context as well as post-translational modifications, including oxidization, phosphorylation, S-nitrosylation, and cleavage, but there should be certain rules in the expression patterns of galectins and their ligand glycoconjugates, possibly related to glucose metabolism in cells.

Natural Products for the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Rapid Development ◽  
New Drugs ◽  
Progressive Degeneration ◽  
Cord Injury ◽  
The Central Nervous System ◽  
And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

T Cells: A Growing Universe of Roles in Neurodegenerative Diseases

2021 ◽  
pp. 107385842110249
Author(s):  
Dallin Dressman ◽  
Wassim Elyaman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Neurodegenerative Diseases ◽  
Human Leukocyte ◽  
Autoimmune Response ◽  
Antigen Specificity ◽  
Risk Genes ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
The Central Nervous System

T cells play a central role in homeostasis and host defense against infectious diseases. T cell dysregulation can lead to recognizing self-antigens as foreign antigens, causing a detrimental autoimmune response. T cell involvement in multiple sclerosis (MS), long understood to be an autoimmune-mediated neurodegenerative disease, is well characterized. More recently, a role for T cells has also been identified for the neurodegenerative diseases Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Interestingly, several alleles and variants of human leukocyte antigen (HLA) genes have been classified as AD and PD risk genes. HLA codes for components of major histocompatibility complex (MHC) class I or class II, both of which are expressed by microglia, the innate immune cells of the central nervous system (CNS). Thus, both microglia and T cells may potentially interact in an antigen-dependent or independent fashion to shape the inflammatory cascade occurring in neurodegenerative diseases. Dissecting the antigen specificity of T cells may lead to new options for disease-modifying treatments in neurodegenerative diseases. Here, we review the current understanding of T cells in neurodegenerative diseases. We summarize the subsets of T cells, their phenotype and potential functions in animal models and in human studies of neurodegenerative diseases.

scholarly journals Precision Medicine in Neurodegenerative Diseases: Some Promising Tips Coming from the microRNAs’ World

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 75 ◽  
Author(s):  
Nicoletta Nuzziello ◽  
Loredana Ciaccia ◽  
Maria Liguori
Keyword(s):  
Neurodegenerative Diseases ◽  
Precision Medicine ◽  
Target Genes ◽  
Drug Disposition ◽  
Therapeutic Potential ◽  
Response To Treatment ◽  
Therapeutic Effects ◽  
Exciting Potential ◽  
The Central Nervous System ◽  
Effective Use

Novel insights in the development of a precision medicine approach for treating the neurodegenerative diseases (NDDs) are provided by emerging advances in the field of pharmacoepigenomics. In this context, microRNAs (miRNAs) have been extensively studied because of their implication in several disorders related to the central nervous system, as well as for their potential role as biomarkers of diagnosis, prognosis, and response to treatment. Recent studies in the field of neurodegeneration reported evidence that drug response and efficacy can be modulated by miRNA-mediated mechanisms. In fact, miRNAs seem to regulate the expression of pharmacology target genes, while approved (conventional and non-conventional) therapies can restore altered miRNAs observed in NDDs. The knowledge of miRNA pharmacoepigenomics may offers new clues to develop more effective treatments by providing novel insights into interindividual variability in drug disposition and response. Recently, the therapeutic potential of miRNAs is gaining increasing attention, and miRNA-based drugs (for cancer) have been under observation in clinical trials. However, the effective use of miRNAs as therapeutic target still needs to be investigated. Here, we report a brief review of representative studies in which miRNAs related to therapeutic effects have been investigated in NDDs, providing exciting potential prospects of miRNAs in pharmacoepigenomics and translational medicine.

Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds

Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 247-261 ◽  
Author(s):  
B.A. Parr ◽  
M.J. Shea ◽  
G. Vassileva ◽  
A.P. McMahon
Keyword(s):  
Limb Development ◽  
Expression Patterns ◽  
Limb Buds ◽  
Expression Studies ◽  
The Family ◽  
The Central Nervous System ◽  
Discrete Domains ◽  
Early Developmental ◽  
The Brain

Mutation and expression studies have implicated the Wnt gene family in early developmental decision making in vertebrates and flies. In a detailed comparative analysis, we have used in situ hybridization of 8.0- to 9.5-day mouse embryos to characterize expression of all ten published Wnt genes in the central nervous system (CNS) and limb buds. Seven of the family members show restricted expression patterns in the brain. At least three genes (Wnt-3, Wnt-3a, and Wnt-7b) exhibit sharp boundaries of expression in the forebrain that may predict subdivisions of the region later in development. In the spinal cord, Wnt-1, Wnt-3, and Wnt-3a are expressed dorsally, Wnt-5a, Wnt-7a, and Wnt-7b more ventrally, and Wnt-4 both dorsally and in the floor plate. In the forelimb primordia, Wnt-3, Wnt-4, Wnt-6 and Wnt-7b are expressed fairly uniformly throughout the limb ectoderm. Wnt-5a RNA is distributed in a proximal to distal gradient through the limb mesenchyme and ectoderm. Along the limb's dorsal-ventral axis, Wnt-5a is expressed in the ventral ectoderm and Wnt-7a in the dorsal ectoderm. We discuss the significance of these patterns of restricted and partially overlapping domains of expression with respect to the putative function of Wnt signalling in early CNS and limb development.

Mouse Hox-3.4: homeobox sequence and embryonic expression patterns compared with other members of the Hox gene network

Development ◽  
1990 ◽  
Vol 109 (2) ◽  
pp. 329-339 ◽  
Author(s):  
S.J. Gaunt ◽  
P.L. Coletta ◽  
D. Pravtcheva ◽  
P.T. Sharpe
Keyword(s):  
Gene Network ◽  
Common Ancestor ◽  
Expression Patterns ◽  
Homeobox Gene ◽  
Predicted Amino Acid Sequence ◽  
Chromosome 15 ◽  
Hox Gene ◽  
The Central Nervous System ◽  
Genomic Organisation

A putative mouse homeobox gene (Hox-3.4) was previously identified 4kb downstream of the Hox-3.3 (Hox-6.1)* gene (Sharpe et al. 1988). We have now sequenced the Hox-3.4 homeobox region. The predicted amino acid sequence shows highest degree of homology in the mouse with Hox-1.3 and -2.1. This, together with similarities in the genomic organisation around these three genes, suggests that they are comembers of a subfamily, derived from a common ancestor. Hox-3.4 appears to be a homologue of the Xenopus Xlhbox5 and human cp11 genes (Fritz and De Robertis, 1988; Simeone et al. 1988). Using a panel of mouse-hamster somatic cell hybrids we have mapped the Hox-3.4 gene to chromosome 15. From the results of in situ hybridization experiments, we describe the distribution of Hox-3.4 transcripts within the 12 1/2 day mouse embryo, and we compare this with the distributions of transcripts shown by seven other members of the Hox gene network. We note three consistencies that underlie the patterns of expression shown by Hox-3.4. First, the anterior limits of Hox-3.4 transcripts in the embryo are related to the position of the Hox-3.4 gene within the Hox-3 locus. Second, the anterior limits of Hox-3.4 expression within the central nervous system are similar to those shown by subfamily homologues Hox-2.1 and Hox-1.3, although the tissue-specific patterns of expression for these three genes show many differences. Third, the patterns of Hox-3.4 expression within the spinal cord and the testis are very similar to those shown by a neighbouring Hox-3 gene (Hox-3.3), but they are quite different from those shown by Hox-1 genes (Hox-1.2, -1.3 and -1.4).

Effect of feeding with bilberry fruit on the expression pattern of αCaMKII in hippocampal neurons in normal and diabetic rats

2017 ◽  
Vol 20 (2) ◽  
pp. 313-319 ◽  
Author(s):  
M. Matysek ◽  
S. Mozel ◽  
R. Szalak ◽  
A. Zacharko-Siembida ◽  
K. Obszańska ◽  
...  
Keyword(s):  
Cognitive Processes ◽  
Hippocampal Neurons ◽  
Negative Impact ◽  
Expression Patterns ◽  
Memory Loss ◽  
Diabetic Rats ◽  
Control Group ◽  
Neuroprotective Effects ◽  
The Central Nervous System ◽  
And Control

Abstract αCaMKII, widely occurring in the central nervous system, plays a significant role in cognitive processes. It is well known that diabetes is a risk factor that may trigger brain atrophy, cognitive dysfunction and finally lead to memory loss. Antioxidants richly present in bilberry fruits are believed to have significant effects on diabetes-related brain dysfunctions mainly due to their abilities to modulate neurotransmitter release that lead to reduction of the negative impact of free radicals on cognitive processes. The aim of the present research was to immunohistochemically investigate the expression patterns of αCaMKII in hippocampal neurons from non-diabetic, diabetic and diabetic rats fed with an extract of bilberry fruit. The obtained results show that in comparison to the control group, in diabetic rats hippocampal neurons immunoreactive (ir) to αCaMKII were swollen and the lengths of the neuronal fibres were reduced. Further study shows that in diabetic rats fed with bilberry fruit, αCaMKII-positive nerve fibres were significantly longer when compared to the groups of diabetic and control rats. Additionally, we observed statistically significant changes in the average larger diameter of αCaMKII-ir hippocampal neurons between groups of diabetic rats (with vs. without supplement of bilberry fruit). The results of the present work suggest that antioxidants present in bilberry fruits influence the morphology of and possibly exhibit beneficial and neuroprotective effects on hippocampal neurons during diabetes. It is likely that changes in the appearance of αCaMKII-expressed hippocampal neurons may reflect the diabetes-evoked rise in Ca2+ level in the cerebral nerve terminals. The present research extends our knowledge of preventive mechanisms for cognitive dysfunctions occurring in the brain during diabetes.

scholarly journals Glial Purinergic Signaling in Neurodegeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Marie J. Pietrowski ◽  
Amr Ahmed Gabr ◽  
Stanislav Kozlov ◽  
David Blum ◽  
Annett Halle ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Glial Cell ◽  
Glial Cells ◽  
Purinergic Signaling ◽  
Expression Patterns ◽  
Specific Expression ◽  
Cell Functions ◽  
Signaling Components ◽  
Therapeutical Options

Purinergic signaling regulates neuronal and glial cell functions in the healthy CNS. In neurodegenerative diseases, purinergic signaling becomes dysregulated and can affect disease-associated phenotypes of glial cells. In this review, we discuss how cell-specific expression patterns of purinergic signaling components change in neurodegeneration and how dysregulated glial purinergic signaling and crosstalk may contribute to disease pathophysiology, thus bearing promising potential for the development of new therapeutical options for neurodegenerative diseases.

scholarly journals Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Fabien Pifferi ◽  
Benoit Laurent ◽  
Mélanie Plourde
Keyword(s):  
Fatty Acids ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Lipid Transport ◽  
Omega 3 ◽  
Blood Brain ◽  
Brain Interface ◽  
The Central Nervous System ◽  
Health And Disease ◽  
The Brain

Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.

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