scholarly journals Understanding the Exchange of Systemic HDL Particles Into the Brain and Vascular Cells Has Diagnostic and Therapeutic Implications for Neurodegenerative Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Juno Van Valkenburgh ◽  
Cristiana Meuret ◽  
Ashley E. Martinez ◽  
Vibha Kodancha ◽  
Victoria Solomon ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Large Family ◽  
Systemic Circulation ◽  
High Density Lipoproteins ◽  
Vascular Cells ◽  
Therapeutic Implications ◽  
Amyloid Metabolism ◽  
The Central Nervous System ◽  
The Brain

High-density lipoproteins (HDLs) are complex, heterogenous lipoprotein particles, consisting of a large family of apolipoproteins, formed in subspecies of distinct shapes, sizes, and functions and are synthesized in both the brain and the periphery. HDL apolipoproteins are important determinants of Alzheimer’s disease (AD) pathology and vascular dementia, having both central and peripheral effects on brain amyloid-beta (Aβ) accumulation and vascular functions, however, the extent to which HDL particles (HLD-P) can exchange their protein and lipid components between the central nervous system (CNS) and the systemic circulation remains unclear. In this review, we delineate how HDL’s structure and composition enable exchange between the brain, cerebrospinal fluid (CSF) compartment, and vascular cells that ultimately affect brain amyloid metabolism and atherosclerosis. Accordingly, we then elucidate how modifications of HDL-P have diagnostic and therapeutic potential for brain vascular and neurodegenerative diseases.

RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neuropsychiatric Disorders ◽  
Extensive Literature ◽  
Ang Ii ◽  
Mas Receptor ◽  
The Central Nervous System ◽  
The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

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.

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.

scholarly journals Expression and distribution of synaptotagmin isoforms in the zebrafish retina

2020 ◽  
Author(s):  
Diane Henry ◽  
Christina Joselevitch ◽  
Gary G. Matthews ◽  
Lonnie P. Wollmuth
Keyword(s):  
Amino Acid ◽  
Large Family ◽  
Amino Acid Residues ◽  
Ribbon Synapses ◽  
The Family ◽  
Class 1 ◽  
The Central Nervous System ◽  
Asynchronous Release ◽  
The Brain

ABSTRACTSynaptotagmins belong to a large family of proteins. While various synaptotagmins have been implicated as Ca2+ sensors for vesicle replenishment and release at conventional synapses, their roles at retinal ribbon synapses remain incompletely understood. Zebrafish is a widely used experimental model for retinal research. We therefore investigated the homology between human, rat, mouse, and zebrafish synaptotagmins 1 to 10 using a bioinformatics approach. We also characterized the expression and distribution of various synaptotagmin (syt) genes in the zebrafish retina using RT-PCR and in situ hybridization, focusing on the family members whose products likely underlie Ca2+-dependent exocytosis in the central nervous system (synaptotagmins 1, 2, 5 and 7). We find that most zebrafish synaptotagmins are well conserved and can be grouped in the same classes as mammalian synaptotagmins, based on crucial amino acid residues needed for coordinating Ca2+ binding and determining phospholipid binding affinity. The only exception is synaptotagmin 1b, which lacks 34 amino acid residues in the C2B domain and is therefore unlikely to bind Ca2+ there. Additionally, the products of zebrafish syt5a and syt5b genes share identity with mammalian class 1 and 5 synaptotagmins. Zebrafish syt1, syt2, syt5 and syt7 paralogues are found in the zebrafish brain, eye, and retina, excepting syt1b, which is only present in the brain. The complementary expression pattern of the remaining paralogues in the retina suggests that syt1a and syt5a may underlie synchronous release and syt7a and syt7b may mediate asynchronous release or other Ca2+ dependent processes in different types of retinal neurons.

scholarly journals Neuregulins in Neurodegenerative Diseases

2021 ◽  
Vol 13 ◽  
Author(s):  
Guan-yong Ou ◽  
Wen-wen Lin ◽  
Wei-jiang Zhao
Keyword(s):  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Neuronal Loss ◽  
Structural Features ◽  
Wide Range ◽  
Erbb Signaling ◽  
The Central Nervous System ◽  
Epidermal Growth ◽  
Erbb Signaling Pathway

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), are typically characterized by progressive neuronal loss and neurological dysfunctions in the nervous system, affecting both memory and motor functions. Neuregulins (NRGs) belong to the epidermal growth factor (EGF)-like family of extracellular ligands and they play an important role in the development, maintenance, and repair of both the central nervous system (CNS) and peripheral nervous system (PNS) through the ErbB signaling pathway. They also regulate multiple intercellular signal transduction and participate in a wide range of biological processes, such as differentiation, migration, and myelination. In this review article, we summarized research on the changes and roles of NRGs in neurodegenerative diseases, especially in AD. We elaborated on the structural features of each NRG subtype and roles of NRG/ErbB signaling networks in neurodegenerative diseases. We also discussed the therapeutic potential of NRGs in the symptom remission of neurodegenerative diseases, which may offer hope for advancing related treatment.

scholarly journals POTENTIAL USE OF SULFORAPHANE AS A NEUROPROTECTOR

2021 ◽  
pp. 125-136
Author(s):  
S. A. Tsiumpala ◽  
K. M. Starchevska ◽  
V. I. Lushchak
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Old Age ◽  
Neurodegenerative Disorders ◽  
Therapeutic Potential ◽  
The Body ◽  
Biologically Active ◽  
Inflammatory Processes ◽  
The Brain ◽  
Potential Use

Introduction. Under normal conditions, oxidative stress and proinflammatory processes are tightly controlled. However, during neuroinflammation and overproduction of reactive oxygen species (ROS), homeostasis is disrup­ted, which may lead to development of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders. Inflammatory processes may result in neurodegenerative disorders. Sulforaphane is an isothiocyanate compound which has potential for treatment of neurodegenerative disorders. Its therapeutic potential is based on the ability to activate transcription of genes, that regulate protective cellular mechanisms. The importance of stu­dying sulforaphane as a neuroprotector is based on the fact, that dementias are the seventh leading cause of death glo­bally and actively progress due to aging of human population. In this review, the anti-inflammatory effects of sulforaphane in the brain and its use as a potential neuroprotector in the treatment of neurodegenerative diseases are discussed. The aim of the study – to review available literature sources on the potential use of sulforaphane to prevent or mitigate neuroinflammation. Conclusions. Economic and technological development of mankind and the improvement of the general qua­lity of life leads to prolongation of human life. But, achievements of longevity give new challenges to humanity. In young age and early adulthood, the organisms can relatively easily maintain homeostasis, then in old age intensification of oxidative stress and inflammatory processes can lead to the development of dementias and mental disorders. What should we do now to save clear mind in old age? In this review, sulforaphane is considered to be a potential neuroprotector. Biologically active supplements and drugs containing sulforaphane can weaken up inflammatory processes in the brain and in the body in general, and therefore they can be used for prevention and treatment of neurodegenerative diseases.

scholarly journals Brain lymphatic drainage system – visualization opportunities and current state of the art

2020 ◽  
Vol 9 (3) ◽  
pp. 81-89
Author(s):  
G. S. Yankova ◽  
O. B. Bogomyakova
Keyword(s):  
Neurodegenerative Diseases ◽  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Drainage System ◽  
Lymphatic Drainage ◽  
Waste Products ◽  
Glymphatic System ◽  
Age Related ◽  
The Central Nervous System ◽  
The Brain

The lymphatic drainage system of the brain is assumed to consist of the lymphatic system and a network of meningeal lymphatic vessels. This system supports brain homeostasis, participates in immune surveillance and presents a new therapeutic target in the treatment of neurological disorders.The article analyzes and systematizes data on the brain lymphatic drainage system. The key components of this system are considered: recently described meningeal lymphatic vessels and their relationship with the glymphatic system, which provides perfusion of the central nervous system with cerebrospinal and interstitial fluids. The lymphatic drainage system helps to maintain water and ion balances of the interstitial fluid and to remove metabolic waste products, assists in reabsorption of macromolecules. Disorders in its work play a crucial role in age-related changes in the brain, the pathogenesis of neurovascular and neurodegenerative diseases, as well as injuries and brain tumors. The review also presents the results of human studies concerning the presence, anatomy and structure of meningeal lymphatic vessels and the glymphatic system. The discovery of the brain lymphatic drainage system has not only changed our understanding of cerebrospinal fluid circulation, but also contributed to understanding the pathology and mechanisms of neurodegenerative diseases.

scholarly journals The Role of GPNMB in Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Marina Saade ◽  
Giovanna Araujo de Souza ◽  
Cristoforo Scavone ◽  
Paula Fernanda Kinoshita
Keyword(s):  
Neurodegenerative Diseases ◽  
Innate Immune ◽  
Inflammatory Conditions ◽  
Pathological Conditions ◽  
Published Evidence ◽  
The Central Nervous System ◽  
Inflammation Resolution ◽  
The Brain ◽  
Lps Treatment

Inflammation is a response to a lesion in the tissue or infection. This process occurs in a specific manner in the central nervous system and is called neuroinflammation, which is involved in neurodegenerative diseases. GPNMB, an endogenous glycoprotein, has been recently related to inflammation and neuroinflammation. GPNMB is highly expressed in macrophages and microglia, which are cells involved with innate immune response in the periphery and the brain, respectively. Some studies have shown increased levels of GPNMB in pro-inflammatory conditions, such as LPS treatment, and in pathological conditions, such as neurodegenerative diseases and cancer. However, the role of GPNMB in inflammation is still not clear. Even though most studies suggest that GPNMB might have an anti-inflammatory role by promoting inflammation resolution, there is evidence that GPNMB could be pro-inflammatory. In this review, we gather and discuss the published evidence regarding this interaction.

scholarly journals Therapeutic Potential of Canine Glial Restricted Progenitors Transplanted in Mouse Model of Demyelinating Disease 

2020 ◽  
Author(s):  
Luiza Stanaszek ◽  
Malgorzata Majchrzak ◽  
Katarzyna Drela ◽  
Piotr Rogujski ◽  
Joanna Sanford ◽  
...  
Keyword(s):  
Demyelinating Disease ◽  
Therapeutic Potential ◽  
Companion Animals ◽  
Therapeutic Benefit ◽  
Posterior Aspect ◽  
Cell Behaviour ◽  
Animal Survival ◽  
The Central Nervous System ◽  
The Brain ◽  
Selection Of

Abstract Background: Dysfunction of glia contributes to the deterioration of the central nervous system in a wide array of neurological disorders, thus global replacement strategies of glia are very attractive. Human glial restricted precursors (hGRPs) transplanted intraventricularly into neonatal mice extensively migrated and rescued lifespan in half of studied mice, while mouse GRPs (mGRPs) presented no therapeutic benefit. We hypothesized that the intrinsic developmental program (IDP) might be one of the main drivers of cell behaviour after grafting, with long migration distance and late myelination for hGRPs, compared to limited migration and early myelination for mGRPs. We studied in the same experimental setting canine GRPs (cGRP) to determine whether their migration, myelination and subsequent therapeutic potential falls between hGRPs and mGRPs. Additional motivation for selection of cGRPs was a potential for use in veterinary medicine due to growing population of dogs as companion animals. Methods: cGRPs were extracted from the brain of dog foetuses. The cells transplanted (4x105 cells) into anterior or posterior aspect of the lateral ventricle (LV) of neonatal, immunodeficient, dysmyelinated mice (shiverer, MBPshi/shi, rag2-/-). Outcome measures included early cell biodistribution, animal survival and myelination assessed with MRI, immunohistochemistry and electron microscopy. Results: Grafting of cGRP into posterior LV significantly extended animal survival, while no benefit was observed after anterior LV transplantation. In contrast, myelination of the corpus callosum was more prominent in anteriorly transplanted animals. Conclusions: The extended survival of animals after transplantation of cGRPs could be explained by the vicinity of transplant near the brain stem.

scholarly journals Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma

2021 ◽  
Vol 12 ◽  
Author(s):  
Luigi Manni ◽  
Giorgio Conti ◽  
Antonio Chiaretti ◽  
Marzia Soligo
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurodegenerative Diseases ◽  
Brain Parenchyma ◽  
Delivery Methods ◽  
Nerve Growth ◽  
The Central Nervous System ◽  
Cholinergic Phenotype ◽  
Preclinical And Clinical Studies ◽  
The Brain

Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromised during the development of AD. Subsequently, the use of NGF was put forward to treat a broader spectrum of neurological conditions affecting the central nervous system, such as Parkinson’s disease, degenerative retinopathies, severe brain traumas and neurodevelopmental dysfunctions. While supported by solid rational assumptions, the progress of a pharmacology founded on these hypotheses has been hampered by the difficulty of conveying NGF towards the brain parenchyma without resorting to invasive and risky delivery methods. At the end of the last century, it was shown that NGF administered intranasally to the olfactory epithelium was able to spread into the brain parenchyma. Notably, after such delivery, pharmacologically relevant concentration of exogenous NGF was found in brain areas located at considerable distances from the injection site along the rostral-caudal axis. These observations paved the way for preclinical characterization and clinical trials on the efficacy of intranasal NGF for the treatment of neurodegenerative diseases and of the consequences of brain trauma. In this review, a summary of the preclinical and clinical studies published to date will be attempted, as well as a discussion about the mechanisms underlying the efficacy and the possible development of the pharmacology based on intranasal conveyance of NGF to the brain.

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