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 Neural Stem Cell Transplantation for Neurodegenerative Diseases

2020 ◽  
Vol 21 (9) ◽  
pp. 3103 ◽  
Author(s):  
Roberta De Gioia ◽  
Fabio Biella ◽  
Gaia Citterio ◽  
Federica Rizzo ◽  
Elena Abati ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neurodegenerative Diseases ◽  
Neural Stem Cell ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Clinical Settings ◽  
Therapeutic Effects ◽  
Cell Therapies ◽  
Effective Therapeutic Strategy ◽  
The Central Nervous System

Neurodegenerative diseases are disabling and fatal neurological disorders that currently lack effective treatment. Neural stem cell (NSC) transplantation has been studied as a potential therapeutic approach and appears to exert a beneficial effect against neurodegeneration via different mechanisms, such as the production of neurotrophic factors, decreased neuroinflammation, enhanced neuronal plasticity and cell replacement. Thus, NSC transplantation may represent an effective therapeutic strategy. To exploit NSCs’ potential, some of their essential biological characteristics must be thoroughly investigated, including the specific markers for NSC subpopulations, to allow profiling and selection. Another key feature is their secretome, which is responsible for the regulation of intercellular communication, neuroprotection, and immunomodulation. In addition, NSCs must properly migrate into the central nervous system (CNS) and integrate into host neuronal circuits, enhancing neuroplasticity. Understanding and modulating these aspects can allow us to further exploit the therapeutic potential of NSCs. Recent progress in gene editing and cellular engineering techniques has opened up the possibility of modifying NSCs to express select candidate molecules to further enhance their therapeutic effects. This review summarizes current knowledge regarding these aspects, promoting the development of stem cell therapies that could be applied safely and effectively in clinical settings.

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 The Functional Roles of Curcumin on Astrocytes in Neurodegenerative Diseases

2021 ◽  
pp. 1-11
Author(s):  
Amir Mohammadi ◽  
Abasalt Hosseinzadeh Colagar ◽  
Ayeh Khorshidian ◽  
Seyed Mohammad Amini
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Essential Role ◽  
Neurological Dysfunction ◽  
Therapeutic Effects ◽  
Functional Roles ◽  
Correct Function ◽  
The Central Nervous System ◽  
Lateral Sclerosis ◽  
Brain Homeostasis

Progressive abnormality and loss of axons and neurons in the central nervous system (CNS) cause neurodegenerative diseases (NDs). Protein misfolding and its collection are the most important pathological features of NDs. Astrocytes are the most plentiful cells in the mammalian CNS (about 20–40% of the human brain) and have several central functions in the maintenance of the health and correct function of the CNS. Astrocytes have an essential role in the preservation of brain homeostasis, and it is not surprising that these multifunctional cells have been implicated in the onset and progression of several NDs. Thus, they become an exciting target for the study of NDs. Over almost 15 years, it was revealed that curcumin has several therapeutic effects in a wide variety of diseases’ treatment. Curcumin is a valuable ingredient present in turmeric spice and has several essential roles, including those which are anticarcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, anti-inflammatory, antioxidant, chemopreventive, chemotherapeutic, and anti-infectious. Furthermore, curcumin can suppress inflammation; promote angiogenesis; and treat diabetes, pulmonary problems, and neurological dysfunction. Here, we review the effects of curcumin on astrocytes in NDs, with a focus on Alzheimer’s disease, Parkinson’s disease, multiple scleroses, Huntington’s disease, and amyotrophic lateral sclerosis.

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.

scholarly journals Combating Neurodegenerative Diseases with the Plant Alkaloid Berberine: Molecular Mechanisms and Therapeutic Potential

2019 ◽  
Vol 17 (6) ◽  
pp. 563-579 ◽  
Author(s):  
Dahua Fan ◽  
Liping Liu ◽  
Zhengzhi Wu ◽  
Meiqun Cao
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Apoptotic Cell ◽  
Isoquinoline Alkaloid ◽  
Therapeutic Approaches ◽  
Current State ◽  
Progressive Degeneration ◽  
The Central Nervous System ◽  
Low Toxicity

Neurodegenerative diseases are among the most serious health problems affecting millions of people worldwide. Such diseases are characterized by a progressive degeneration and / or death of neurons in the central nervous system. Currently, there are no therapeutic approaches to cure or even halt the progression of neurodegenerative diseases. During the last two decades, much attention has been paid to the neuroprotective and anti-neurodegenerative activities of compounds isolated from natural products with high efficacy and low toxicity. Accumulating evidence indicates that berberine, an isoquinoline alkaloid isolated from traditional Chinese medicinal herbs, may act as a promising anti-neurodegenerative agent by inhibiting the activity of the most important pathogenic enzymes, ameliorating intracellular oxidative stress, attenuating neuroinflammation, triggering autophagy and protecting neurons against apoptotic cell death. This review attempts to summarize the current state of knowledge regarding the therapeutic potential of berberine against neurodegenerative diseases, with a focus on the molecular mechanisms that underlie its effects on Alzheimer’s, Parkinson’s and Huntington’s diseases.

Antioxidant Effect of Flavonoids Present in Euterpe oleracea Martius and Neurodegenerative Diseases: A Literature Review

2019 ◽  
Vol 19 (2) ◽  
pp. 75-99 ◽  
Author(s):  
Nayana Keyla Seabra de Oliveira ◽  
Marcos Rafael Silva Almeida ◽  
Franco Márcio Maciel Pontes ◽  
Mariana Pegrucci Barcelos ◽  
Carlos Henrique Tomich de Paula da Silva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
In Vivo Studies ◽  
Euterpe Oleracea ◽  
Case Review ◽  
The Central Nervous System

Introduction:Neurodegenerative diseases (NDDs) are progressive, directly affecting the central nervous system (CNS), the most common and recurrent are Alzheimer's disease (AD) and Parkinson's disease (PD). One factor frequently mentioned in the etiology of NDDs is the generation of free radicals and oxidative stress, producing cellular damages. Studies have shown that the consumption of foods rich in polyphenols, especially those of the flavonoid class, has been related to the low risk in the development of several diseases. Due to the antioxidant properties present in the food, a fruit that has been gaining prominence among these foods is the Euterpe oleracea Mart. (açaí), because it presents in its composition significant amounts of a subclass of the flavonoids, the anthocyanins.Methods:In the case review, the authors receive a basic background on the most common NDDs, oxidative stress and antioxidants. In addition, revisiting the various studies related to NDDs, including flavonoids and consumption of açaí.Results:Detailed analysis of the recently reported case studies reveal that dietary consumption of flavonoid-rich foods, such as açaí fruits, suggests the efficacy to attenuate neurodegeneration and prevent or reverse the age-dependent deterioration of cognitive function.Conclusion:This systematic review points out that flavonoids presenting in açaí have the potential for the treatment of diseases such as PD and AD and are candidates for drugs in future clinical research. However, there is a need for in vitro and in vivo studies with polyphenol that prove and ratify the therapeutic potential of this fruit for several NDDs.

scholarly journals Erythropoietin as a Neuroprotective Molecule: An Overview of Its Therapeutic Potential in Neurodegenerative Diseases

ASN NEURO ◽  
2019 ◽  
Vol 11 ◽  
pp. 175909141987142 ◽  
Author(s):  
Federica Rey ◽  
Alice Balsari ◽  
Toniella Giallongo ◽  
Sara Ottolenghi ◽  
Anna M. Di Giulio ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Erythropoietin Receptor ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Erythroid Progenitor ◽  
Beneficial Effects ◽  
Cord Injury

Erythropoietin (EPO) is a cytokine mainly induced in hypoxia conditions. Its major production site is the kidney. EPO primarily acts on the erythroid progenitor cells in the bone marrow. More and more studies are highlighting its secondary functions, with a crucial focus on its role in the central nervous system. Here, EPO may interact with up to four distinct isoforms of its receptor (erythropoietin receptor [EPOR]), activating different signaling cascades with roles in neuroprotection and neurogenesis. Indeed, the EPO/EPOR axis has been widely studied in the neurodegenerative diseases field. Its potential therapeutic effects have been evaluated in multiple disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, spinal cord injury, as well as brain ischemia, hypoxia, and hyperoxia. EPO is showing great promise by counteracting secondary neuroinflammatory processes, reactive oxygen species imbalance, and cell death in these diseases. Multiple studies have been performed both in vitro and in vivo, characterizing the mechanisms through which EPO exerts its neurotrophic action. In some cases, clinical trials involving EPO have been performed, highlighting its therapeutic potential. Together, all these works indicate the potential beneficial effects of EPO.

scholarly journals Nanoparticles: A Hope for the Treatment of Inflammation in CNS

2021 ◽  
Vol 12 ◽  
Author(s):  
Feng-Dan Zhu ◽  
Yu-Jiao Hu ◽  
Lu Yu ◽  
Xiao-Gang Zhou ◽  
Jian-Ming Wu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Therapeutic Agent ◽  
Therapeutic Effects ◽  
Therapeutic Tool ◽  
Promising Strategy ◽  
The Central Nervous System ◽  
Inflammatory Drugs ◽  
Lateral Sclerosis ◽  
Pro Inflammatory Cytokines

Neuroinflammation, an inflammatory response within the central nervous system (CNS), is a main hallmark of common neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), among others. The over-activated microglia release pro-inflammatory cytokines, which induces neuronal death and accelerates neurodegeneration. Therefore, inhibition of microglia over-activation and microglia-mediated neuroinflammation has been a promising strategy for the treatment of neurodegenerative diseases. Many drugs have shown promising therapeutic effects on microglia and inflammation. However, the blood–brain barrier (BBB)—a natural barrier preventing brain tissue from contact with harmful plasma components—seriously hinders drug delivery to the microglial cells in CNS. As an emerging useful therapeutic tool in CNS-related diseases, nanoparticles (NPs) have been widely applied in biomedical fields for use in diagnosis, biosensing and drug delivery. Recently, many NPs have been reported to be useful vehicles for anti-inflammatory drugs across the BBB to inhibit the over-activation of microglia and neuroinflammation. Therefore, NPs with good biodegradability and biocompatibility have the potential to be developed as an effective and minimally invasive carrier to help other drugs cross the BBB or as a therapeutic agent for the treatment of neuroinflammation-mediated neurodegenerative diseases. In this review, we summarized various nanoparticles applied in CNS, and their mechanisms and effects in the modulation of inflammation responses in neurodegenerative diseases, providing insights and suggestions for the use of NPs in the treatment of neuroinflammation-related neurodegenerative diseases.

scholarly journals Involvement of Astrocytes and microRNA Dysregulation in Neurodegenerative Diseases: From Pathogenesis to Therapeutic Potential

2021 ◽  
Vol 14 ◽  
Author(s):  
Yang Bai ◽  
Xing Su ◽  
Lianhua Piao ◽  
Zheng Jin ◽  
Rihua Jin
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Neuronal Loss ◽  
Novel Approach ◽  
Wide Range ◽  
Antigen Transfer ◽  
The Central Nervous System ◽  
Microrna Dysregulation ◽  
Slow Onset

Astrocytes are the most widely distributed and abundant glial cells in the central nervous system (CNS). Neurodegenerative diseases (NDDs) are a class of diseases with a slow onset, progressive progression, and poor prognosis. Common clinical NDDs include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Although these diseases have different etiologies, they are all associated with neuronal loss and pathological dysfunction. Accumulating evidence indicates that neurotransmitters, neurotrophic factors, and toxic metabolites that are produced and released by activated astrocytes affect and regulate the function of neurons at the receptor, ion channel, antigen transfer, and gene transcription levels in the pathogenesis of NDDs. MicroRNAs (miRNAs) are a group of small non-coding RNAs that play a wide range of biological roles by regulating the transcription and post-transcriptional translation of target mRNAs to induce target gene expression and silencing. Recent studies have shown that miRNAs participate in the pathogenesis of NDDs by regulating astrocyte function through different mechanisms and may be potential targets for the treatment of NDDs. Here, we review studies of the role of astrocytes in the pathogenesis of NDDs and discuss possible mechanisms of miRNAs in the regulation of astrocyte function, suggesting that miRNAs may be targeted as a novel approach for the treatment of NDDs.

scholarly journals Epilepsy in Neurodegenerative Diseases: Related Drugs and Molecular Pathways

2021 ◽  
Vol 14 (10) ◽  
pp. 1057
Author(s):  
Amanda Cano ◽  
Elena Fonseca ◽  
Miren Ettcheto ◽  
Elena Sánchez-López ◽  
Itziar de Rojas ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Refractory Epilepsy ◽  
Therapeutic Potential ◽  
Epileptic Seizures ◽  
Molecular Pathways ◽  
Molecular Processes ◽  
Main Hypothesis ◽  
Neurotoxic Effects ◽  
The Central Nervous System ◽  
The Common

Epilepsy is a chronic disease of the central nervous system characterized by an electrical imbalance in neurons. It is the second most prevalent neurological disease, with 50 million people affected around the world, and 30% of all epilepsies do not respond to available treatments. Currently, the main hypothesis about the molecular processes that trigger epileptic seizures and promote the neurotoxic effects that lead to cell death focuses on the exacerbation of the glutamate pathway and the massive influx of Ca2+ into neurons by different factors. However, other mechanisms have been proposed, and most of them have also been described in other neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, or multiple sclerosis. Interestingly, and mainly because of these common molecular links and the lack of effective treatments for these diseases, some antiseizure drugs have been investigated to evaluate their therapeutic potential in these pathologies. Therefore, in this review, we thoroughly investigate the common molecular pathways between epilepsy and the major neurodegenerative diseases, examine the incidence of epilepsy in these populations, and explore the use of current and innovative antiseizure drugs in the treatment of refractory epilepsy and other neurodegenerative diseases.

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