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 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 The Role of the Inflammasome in Neurodegenerative Diseases

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 953
Author(s):  
Federica Piancone ◽  
Francesca La Rosa ◽  
Ivana Marventano ◽  
Marina Saresella ◽  
Mario Clerici
Keyword(s):  
Neurodegenerative Diseases ◽  
Nlrp3 Inflammasome ◽  
Adaptor Protein ◽  
Neuronal Structure ◽  
Inflammatory Mechanism ◽  
The Central Nervous System ◽  
And Function ◽  
Lateral Sclerosis ◽  
Pro Inflammatory Cytokines

Neurodegenerative diseases are chronic, progressive disorders that occur in the central nervous system (CNS). They are characterized by the loss of neuronal structure and function and are associated with inflammation. Inflammation of the CNS is called neuroinflammation, which has been implicated in most neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Much evidence indicates that these different conditions share a common inflammatory mechanism: the activation of the inflammasome complex in peripheral monocytes and in microglia, with the consequent production of high quantities of the pro-inflammatory cytokines IL-1β and IL-18. Inflammasomes are a group of multimeric signaling complexes that include a sensor Nod-like receptor (NLR) molecule, the adaptor protein ASC, and caspase-1. The NLRP3 inflammasome is currently the best-characterized inflammasome. Multiple signals, which are potentially provided in combination and include endogenous danger signals and pathogens, trigger the formation of an active inflammasome, which, in turn, will stimulate the cleavage and the release of bioactive cytokines including IL-1β and IL-18. In this review, we will summarize results implicating the inflammasome as a pivotal player in the pathogenesis of neurodegenerative diseases and discuss how compounds that hamper the activation of the NLRP3 inflammasome could offer novel therapeutic avenues for these 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.

scholarly journals An Overview of Crucial Dietary Substances and Their Modes of Action for Prevention of Neurodegenerative Diseases

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 576 ◽  
Author(s):  
Lea Pogačnik ◽  
Ajda Ota ◽  
Nataša Poklar Ulrih
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Mechanisms Of Action ◽  
Biological Mechanisms ◽  
Health Concerns ◽  
The Central Nervous System ◽  
Protein Fibrillation ◽  
Endogenous Substances ◽  
Therapeutic Considerations ◽  
Lateral Sclerosis

Neurodegenerative diseases, namely Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis are becoming one of the main health concerns due to the increasing aging of the world’s population. These diseases often share the same biological mechanisms, including neuroinflammation, oxidative stress, and/or protein fibrillation. Recently, there have been many studies published pointing out the possibilities to reduce and postpone the clinical manifestation of these deadly diseases through lifelong consumption of some crucial dietary substances, among which phytochemicals (e.g., polyphenols) and endogenous substances (e.g., acetyl-L-carnitine, coenzyme Q10, n-3 poysaturated fatty acids) showed the most promising results. Another important issue that has been pointed out recently is the availability of these substances to the central nervous system, where they have to be present in high enough concentrations in order to exhibit their neuroprotective properties. As so, such the aim of this review is to summarize the recent findings regarding neuroprotective substances, their mechanisms of action, as well as to point out therapeutic considerations, including their bioavailability and safety for humans.

scholarly journals Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Hyuk Sung Kwon ◽  
Seong-Ho Koh
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Inflammatory Responses ◽  
Therapeutic Drugs ◽  
M1 Phenotype ◽  
The Central Nervous System ◽  
The Relationship ◽  
Lateral Sclerosis ◽  
M2 Phenotype

AbstractNeuroinflammation is associated with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system. The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxic (M1-phenotype microglia and A1-phenotype astrocytes) or neuroprotective (M2-phenotype microglia and A2-phenotype astrocytes). However, this dichotomized classification may not reflect the various phenotypes of microglia and astrocytes. The relationship between these activated glial cells is also very complicated, and the phenotypic distribution can change, based on the progression of neurodegenerative diseases. A better understanding of the roles of microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies. In this review, we discuss the roles of inflammatory response in neurodegenerative diseases, focusing on the contributions of microglia and astrocytes and their relationship. In addition, we discuss biomarkers to measure neuroinflammation and studies on therapeutic drugs that can modulate neuroinflammation.

Current Limitations in the Treatment of Parkinson’s and Alzheimer’s Diseases: State-of-the-Art and Future Perspective of Polymeric Carriers

2019 ◽  
Vol 25 (41) ◽  
pp. 5755-5771 ◽  
Author(s):  
Chiara Tonda-Turo ◽  
Nicola Origlia ◽  
Clara Mattu ◽  
Alice Accorroni ◽  
Valeria Chiono
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Local Drug Delivery ◽  
Future Perspective ◽  
Non Invasive ◽  
Therapeutic Drugs ◽  
Parkinson’S Diseases ◽  
Polymeric Carriers ◽  
The Central Nervous System ◽  
The Moment

Alzheimer’s and Parkinson’s diseases are the most common neurodegenerative diseases worldwide and their incidence is increasing due to the aging population. At the moment, the available therapies are not disease modifying and have several limitations, some of which are discussed in this review. One of the main limitations of these treatments is the low concentration that drugs reach in the central nervous system after systemic administration. Indeed, the presence of biological barriers, particularly the blood-brain barrier (BBB), hinders the effective drug delivery to the brain, reducing the potential benefit coming from the administration of the medication. In this review, the mechanisms of transport across the BBB and new methods to improve drug passage across the BBB are discussed. These methods include non-invasive solutions such as intranasal and intravitreal administration, and the use of nanotechnology solutions based on polymeric carriers when the drug is intravenously injected, orally taken for intestine adsorption or delivered through the dermal mucosa. Also, it provides an analysis of more invasive solutions that include intracranially injected hydrogels and implanted devices for local drug delivery. Efforts in finding new therapeutic drugs blocking neurodegenerative disease progression or reverting their course should be coupled with efforts addressed to efficient drug delivery systems. Hence, new pharmacology discoveries together with advancements in nanotechnologies and biomaterials for regenerative medicine are required to effectively counteract neurodegenerative diseases.

scholarly journals Microglial Turnover in Ageing-Related Neurodegeneration: Therapeutic Avenue to Intervene in Disease Progression

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 150
Author(s):  
Shofiul Azam ◽  
Md. Ezazul Haque ◽  
In-Su Kim ◽  
Dong-Kug Choi
Keyword(s):  
Neurodegenerative Diseases ◽  
Proinflammatory Cytokines ◽  
Chronic Traumatic Encephalopathy ◽  
Prion Diseases ◽  
Well Being ◽  
Age Related ◽  
The Central Nervous System ◽  
Potential Mode ◽  
Therapeutic Avenue ◽  
Lateral Sclerosis

Microglia are brain-dwelling macrophages and major parts of the neuroimmune system that broadly contribute to brain development, homeostasis, ageing and injury repair in the central nervous system (CNS). Apart from other brain macrophages, they have the ability to constantly sense changes in the brain’s microenvironment, functioning as housekeepers for neuronal well-being and providing neuroprotection in normal physiology. Microglia use a set of genes for these functions that involve proinflammatory cytokines. In response to specific stimuli, they release these proinflammatory cytokines, which can damage and kill neurons via neuroinflammation. However, alterations in microglial functioning are a common pathophysiology in age-related neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s and prion diseases, as well as amyotrophic lateral sclerosis, frontotemporal dementia and chronic traumatic encephalopathy. When their sentinel or housekeeping functions are severely disrupted, they aggravate neuropathological conditions by overstimulating their defensive function and through neuroinflammation. Several pathways are involved in microglial functioning, including the Trem2, Cx3cr1 and progranulin pathways, which keep the microglial inflammatory response under control and promote clearance of injurious stimuli. Over time, an imbalance in this system leads to protective microglia becoming detrimental, initiating or exacerbating neurodegeneration. Correcting such imbalances might be a potential mode of therapeutic intervention in neurodegenerative diseases.

scholarly journals Intersection between Redox Homeostasis and Autophagy: Valuable Insights into Neurodegeneration

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 694
Author(s):  
Hyungsun Park ◽  
Jongyoon Kim ◽  
Chihoon Shin ◽  
Seongju Lee
Keyword(s):  
Neurodegenerative Diseases ◽  
Redox Homeostasis ◽  
Degradation Pathway ◽  
Pharmacological Intervention ◽  
Oxygen Species ◽  
Promising Strategy ◽  
Autophagy Induction ◽  
The Relationship ◽  
The Brain ◽  
Lateral Sclerosis

Autophagy, a main degradation pathway for maintaining cellular homeostasis, and redox homeostasis have recently been considered to play protective roles in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Increased levels of reactive oxygen species (ROS) in neurons can induce mitochondrial damage and protein aggregation, thereby resulting in neurodegeneration. Oxidative stress is one of the major activation signals for the induction of autophagy. Upon activation, autophagy can remove ROS, damaged mitochondria, and aggregated proteins from the cells. Thus, autophagy can be an effective strategy to maintain redox homeostasis in the brain. However, the interaction between redox homeostasis and autophagy is not clearly elucidated. In this review, we discuss recent studies on the relationship between redox homeostasis and autophagy associated with neurodegenerative diseases and propose that autophagy induction through pharmacological intervention or genetic activation might be a promising strategy to treat these disorders.

scholarly journals Exosomes: Innocent Bystanders or Critical Culprits in Neurodegenerative Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Margarida Beatriz ◽  
Rita Vilaça ◽  
Carla Lopes
Keyword(s):  
Neurodegenerative Diseases ◽  
Intercellular Communication ◽  
Prion Diseases ◽  
Genetic Material ◽  
Cell Communication ◽  
Protein Aggregates ◽  
Potential Benefits ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Extracellular vesicles (EVs) are nano-sized membrane-enclosed particles released by cells that participate in intercellular communication through the transfer of biologic material. EVs include exosomes that are small vesicles that were initially associated with the disposal of cellular garbage; however, recent findings point toward a function as natural carriers of a wide variety of genetic material and proteins. Indeed, exosomes are vesicle mediators of intercellular communication and maintenance of cellular homeostasis. The role of exosomes in health and age-associated diseases is far from being understood, but recent evidence implicates exosomes as causative players in the spread of neurodegenerative diseases. Cells from the central nervous system (CNS) use exosomes as a strategy not only to eliminate membranes, toxic proteins, and RNA species but also to mediate short and long cell-to-cell communication as carriers of important messengers and signals. The accumulation of protein aggregates is a common pathological hallmark in many neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. Protein aggregates can be removed and delivered to degradation by the endo-lysosomal pathway or can be incorporated in multivesicular bodies (MVBs) that are further released to the extracellular space as exosomes. Because exosome transport damaged cellular material, this eventually contributes to the spread of pathological misfolded proteins within the brain, thus promoting the neurodegeneration process. In this review, we focus on the role of exosomes in CNS homeostasis, their possible contribution to the development of neurodegenerative diseases, the usefulness of exosome cargo as biomarkers of disease, and the potential benefits of plasma circulating CNS-derived exosomes.

scholarly journals Astroglial Connexins in Neurodegenerative Diseases

2021 ◽  
Vol 14 ◽  
Author(s):  
Xiaomin Huang ◽  
Yixun Su ◽  
Nan Wang ◽  
Hui Li ◽  
Zhigang Li ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuronal Function ◽  
Gap Junction Channels ◽  
Normal Functions ◽  
Functional Remodeling ◽  
The Central Nervous System ◽  
Key Aspects ◽  
And Function ◽  
Lateral Sclerosis

Astrocytes play a crucial role in the maintenance of the normal functions of the Central Nervous System (CNS). During the pathogenesis of neurodegenerative diseases, astrocytes undergo morphological and functional remodeling, a process called reactive astrogliosis, in response to the insults to the CNS. One of the key aspects of the reactive astrocytes is the change in the expression and function of connexins. Connexins are channel proteins that highly expressed in astrocytes, forming gap junction channels and hemichannels, allowing diffusional trafficking of small molecules. Alterations of astrocytic connexin expression and function found in neurodegenerative diseases have been shown to affect the disease progression by changing neuronal function and survival. In this review, we will summarize the role of astroglial connexins in neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Also, we will discuss why targeting connexins can be a plausible therapeutic strategy to manage these neurodegenerative diseases.

Sign in / Sign up

Export Citation Format

Share Document