scholarly journals Nanotechnology-mediated crossing of two impermeable membranes to modulate the stars of the neurovascular unit for neuroprotection

2018 ◽  
Vol 115 (52) ◽  
pp. E12333-E12342 ◽  
Author(s):  
Bapurao Surnar ◽  
Uttara Basu ◽  
Bhabatosh Banik ◽  
Anis Ahmad ◽  
Brian Marples ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Neurodegenerative Diseases ◽  
Neurovascular Unit ◽  
Neuronal Cell ◽  
Capillary Endothelium ◽  
Target Cells ◽  
Full Potential ◽  
Beneficial Effects ◽  
Neuroprotective Actions ◽  
The Brain

The success of nanoparticle-mediated delivery of antioxidant and antiinflammatory-based neuroprotectants to the brain to improve neuronal functions in neurodegenerative diseases has demonstrated lesser impact instead of achieving its full potential. We hypothesized that these failures were due to a combination of parameters, such as: (i) unavailability of a delivery vehicle, which can reproducibly and efficiently transport through the brain capillary endothelium; (ii) inefficient uptake of therapeutic nanoparticles in the neuronal cell population; and (iii) limited ability of a single nanoparticle to cross the two most-impermeable biological barriers, the blood–brain barrier and mitochondrial double membrane, so that a nanoparticle can travel through the brain endothelial barrier to the mitochondria of target cells where oxidative damage is localized. Herein, we demonstrate optimization of a biodegradable nanoparticle for efficient brain accumulation and protection of astrocytes from oxidative damage and mitochondrial dysfunctions to enhance the neuroprotection ability of astrocytes toward neurons using neurodegeneration characteristics in SOD1G93A rats. This biodegradable nanomedicine platform with the ability to accumulate in the brain has the potential to bring beneficial effects in neurodegenerative diseases by modulating the stars, astrocytes in the brain, to enhance their neuroprotective actions.

scholarly journals Coenzyme Q10 and its effects in the treatment of neurodegenerative diseases

2009 ◽  
Vol 45 (4) ◽  
pp. 607-618 ◽  
Author(s):  
Graciela Cristina dos Santos ◽  
Lusânia Maria Greggi Antunes ◽  
Antonio Cardozo dos Santos ◽  
Maria de Lourdes Pires Bianchi
Keyword(s):  
Neurodegenerative Diseases ◽  
Health Risks ◽  
Coenzyme Q10 ◽  
Cellular Respiration ◽  
Irreversible Loss ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Electron Transportation ◽  
The Brain ◽  
Lateral Sclerosis

According to clinical and pre-clinical studies, oxidative stress and its consequences may be the cause or, at least, a contributing factor, to a large number of neurodegenerative diseases. These diseases include common and debilitating disorders, characterized by progressive and irreversible loss of neurons in specific regions of the brain. The most common neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Coenzyme Q10 (CoQ10) has been extensively studied since its discovery in 1957. It is a component of the electron transportation chain and participates in aerobic cellular respiration, generating energy in the form of adenosine triphosphate (ATP). The property of CoQ10 to act as an antioxidant or a pro-oxidant, suggests that it also plays an important role in the modulation of redox cellular status under physiological and pathological conditions, also performing a role in the ageing process. In several animal models of neurodegenerative diseases, CoQ10 has shown beneficial effects in reducing disease progression. However, further studies are needed to assess the outcome and effectiveness of CoQ10 before exposing patients to unnecessary health risks at significant costs.

scholarly journals Neuroprotective Effect of Antioxidants in the Brain

2020 ◽  
Vol 21 (19) ◽  
pp. 7152 ◽  
Author(s):  
Kyung Hee Lee ◽  
Myeounghoon Cha ◽  
Bae Hwan Lee
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Intracellular Signaling ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
High Energy ◽  
Antioxidant Compounds ◽  
The Brain

The brain is vulnerable to excessive oxidative insults because of its abundant lipid content, high energy requirements, and weak antioxidant capacity. Reactive oxygen species (ROS) increase susceptibility to neuronal damage and functional deficits, via oxidative changes in the brain in neurodegenerative diseases. Overabundance and abnormal levels of ROS and/or overload of metals are regulated by cellular defense mechanisms, intracellular signaling, and physiological functions of antioxidants in the brain. Single and/or complex antioxidant compounds targeting oxidative stress, redox metals, and neuronal cell death have been evaluated in multiple preclinical and clinical trials as a complementary therapeutic strategy for combating oxidative stress associated with neurodegenerative diseases. Herein, we present a general analysis and overview of various antioxidants and suggest potential courses of antioxidant treatments for the neuroprotection of the brain from oxidative injury. This review focuses on enzymatic and non-enzymatic antioxidant mechanisms in the brain and examines the relative advantages and methodological concerns when assessing antioxidant compounds for the treatment of neurodegenerative disorders.

scholarly journals Neuronal Cell Death Mechanisms in Major Neurodegenerative Diseases

2018 ◽  
Vol 19 (10) ◽  
pp. 3082 ◽  
Author(s):  
Hao Chi ◽  
Hui-Yun Chang ◽  
Tzu-Kang Sang
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Alpha Synuclein ◽  
Adult Brain ◽  
Pathological Feature ◽  
The Central Nervous System ◽  
Cell Death Mechanisms ◽  
The Brain

Neuronal cell death in the central nervous system has always been a challenging process to decipher. In normal physiological conditions, neuronal cell death is restricted in the adult brain, even in aged individuals. However, in the pathological conditions of various neurodegenerative diseases, cell death and shrinkage in a specific region of the brain represent a fundamental pathological feature across different neurodegenerative diseases. In this review, we will briefly go through the general pathways of cell death and describe evidence for cell death in the context of individual common neurodegenerative diseases, discussing our current understanding of cell death by connecting with renowned pathogenic proteins, including Tau, amyloid-beta, alpha-synuclein, huntingtin and TDP-43.

scholarly journals Engineered Extracellular Vesicles/Exosomes as a New Tool against Neurodegenerative Diseases

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 529 ◽  
Author(s):  
Flavia Ferrantelli ◽  
Chiara Chiozzini ◽  
Patrizia Leone ◽  
Francesco Manfredi ◽  
Maurizio Federico
Keyword(s):  
Neurodegenerative Diseases ◽  
Extracellular Vesicles ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Protein Aggregates ◽  
Target Cells ◽  
Abnormal Protein ◽  
Neuronal Proteins ◽  
The Central Nervous System

Neurodegenerative diseases are commonly generated by intracellular accumulation of misfolded/aggregated mutated proteins. These abnormal protein aggregates impair the functions of mitochondria and induce oxidative stress, thereby resulting in neuronal cell death. In turn, neuronal damage induces chronic inflammation and neurodegeneration. Thus, reducing/eliminating these abnormal protein aggregates is a priority for any anti-neurodegenerative therapeutic approach. Although several antibodies against mutated neuronal proteins have been already developed, how to efficiently deliver them inside the target cells remains an unmet issue. Extracellular vesicles/exosomes incorporating intrabodies against the pathogenic products would be a tool for innovative therapeutic approaches. In this review/perspective article, we identify and describe the major molecular targets associated with neurodegenerative diseases, as well as the antibodies already developed against them. Finally, we propose a novel targeting strategy based on the endogenous engineering of extracellular vesicles/exosomes constitutively released by cells of the central nervous system.

scholarly journals Beneficial Effects ofTeucrium poliumand Metformin on Diabetes-Induced Memory Impairments and Brain Tissue Oxidative Damage in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
S. Mojtaba Mousavi ◽  
Saeed Niazmand ◽  
Mahmoud Hosseini ◽  
Zarha Hassanzadeh ◽  
Hamid Reza Sadeghnia ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Lipid Peroxides ◽  
Diabetic Group ◽  
Control Group ◽  
Hydroalcoholic Extract ◽  
Memory Impairments ◽  
Beneficial Effects ◽  
Teucrium Polium ◽  
The Brain ◽  
Brain Tissues

Objective.The effects of hydroalcoholic extract ofTeucrium poliumand metformin on diabetes-induced memory impairment and brain tissues oxidative damage were investigated.Methods.The rats were divided into: (1) Control, (2) Diabetic, (3) Diabetic-Extract 100 (Dia-Ext 100), (4) Diabetic-Extract 200 (Dia-Ext 200), (5) Diabetic-Extract 400 (Dia-Ext 400), and (6) Diabetic-Metformin (Dia-Met). Groups 3–6 were treated by 100, 200, and 400 mg/kg of the extract or metformin, respectively, for 6 weeks (orally).Results. In passive avoidance test, the latency to enter the dark compartment in Diabetic group was lower than that of Control group (P<0.01). In Dia-Ext 100, Dia-Ext 200, and Dia-Ext 400 and Metformin groups, the latencies were higher than those of Diabetic group (P<0.01). Lipid peroxides levels (reported as malondialdehyde, MDA, concentration) in the brain of Diabetic group were higher than Control (P<0.001). Treatment by all doses of the extract and metformin decreased the MDA concentration (P<0.01).Conclusions.The results of present study showed that metformin and the hydroalcoholic extract ofTeucrium poliumprevent diabetes-induced memory deficits in rats. Protection against brain tissues oxidative damage might have a role in the beneficial effects of the extract and metformin.

scholarly journals Therapeutic Approach to Neurodegenerative Diseases by Medical Gases: Focusing on Redox Signaling and Related Antioxidant Enzymes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kyota Fujita ◽  
Megumi Yamafuji ◽  
Yusaku Nakabeppu ◽  
Mami Noda
Keyword(s):  
Antioxidant Enzymes ◽  
Oxidative Damage ◽  
Neurodegenerative Diseases ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Heme Oxygenase 1 ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Therapeutic Uses

Oxidative stress in the central nervous system is strongly associated with neuronal cell death in the pathogenesis of several neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In order to overcome the oxidative damage, there are some protective signaling pathways related to transcriptional upregulation of antioxidant enzymes, such as heme oxygenase-1 (HO-1) and superoxide dismutase (SOD)-1/-2. Their expression is regulated by several transcription factors and/or cofactors like nuclear factor-erythroid 2 (NF-E2) related factor 2 (Nrf2) and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α). These antioxidant enzymes are associated with, and in some cases, prevent neuronal death in animal models of neurodegenerative diseases. They are activated by endogenous mediators and phytochemicals, and also by several gases such as carbon monoxide (CO), hydrogen sulphide (H2S), and hydrogen (H2). These might thereby protect the brain from severe oxidative damage and resultant neurodegenerative diseases. In this paper, we discuss how the expression levels of these antioxidant enzymes are regulated. We also introduce recent advances in the therapeutic uses of medical gases against neurodegenerative diseases.

scholarly journals Stem Cell Therapy for Cerebral Ischemia: From Basic Science to Clinical Applications

2012 ◽  
Vol 32 (7) ◽  
pp. 1317-1331 ◽  
Author(s):  
Koji Abe ◽  
Toru Yamashita ◽  
Shunya Takizawa ◽  
Satoshi Kuroda ◽  
Hiroyuki Kinouchi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Neurodegenerative Diseases ◽  
Stem Cell Therapy ◽  
Basic Science ◽  
Cell Tracking ◽  
Neurovascular Unit ◽  
Clinical Applications ◽  
The Brain

Recent stem cell technology provides a strong therapeutic potential not only for acute ischemic stroke but also for chronic progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis with neuroregenerative neural cell replenishment and replacement. In addition to resident neural stem cell activation in the brain by neurotrophic factors, bone marrow stem cells (BMSCs) can be mobilized by granulocyte-colony stimulating factor for homing into the brain for both neurorepair and neuroregeneration in acute stroke and neurodegenerative diseases in both basic science and clinical settings. Exogenous stem cell transplantation is also emerging into a clinical scene from bench side experiments. Early clinical trials of intravenous transplantation of autologous BMSCs are showing safe and effective results in stroke patients. Further basic sciences of stem cell therapy on a neurovascular unit and neuroregeneration, and further clinical advancements on scaffold technology for supporting stem cells and stem cell tracking technology such as magnetic resonance imaging, single photon emission tomography or optical imaging with near-infrared could allow stem cell therapy to be applied in daily clinical applications in the near future.

scholarly journals Combination of Alanine and Glutathione as Targeting Ligands of Nanoparticles Enhances Cargo Delivery into the Cells of the Neurovascular Unit

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 635
Author(s):  
Gergő Porkoláb ◽  
Mária Mészáros ◽  
András Tóth ◽  
Anikó Szecskó ◽  
András Harazin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cultured Cells ◽  
Neurological Diseases ◽  
Neurovascular Unit ◽  
Cell Types ◽  
Target Cells ◽  
Brain Endothelial Cells ◽  
Multiple Ligands ◽  
The Brain

Inefficient drug delivery across the blood–brain barrier (BBB) and into target cells in the brain hinders the treatment of neurological diseases. One strategy to increase the brain penetration of drugs is to use vesicular nanoparticles functionalized with multiple ligands of BBB transporters as vehicles. Once within the brain, however, drugs must also be able to reach their therapeutic targets in the different cell types. It is, therefore, favorable if such nanocarriers are designed that can deliver their cargo not only to brain endothelial cells, but to other cell types as well. Here, we show that alanine-glutathione dual-targeting of niosomes enhances the delivery of a large protein cargo into cultured cells of the neurovascular unit, namely brain endothelial cells, pericytes, astrocytes and neurons. Furthermore, using metabolic and endocytic inhibitors, we show that the cellular uptake of niosomes is energy-dependent and is partially mediated by endocytosis. Finally, we demonstate the ability of our targeted nanovesicles to deliver their cargo into astroglial cells after crossing the BBB in vitro. These data indicate that dual-labeling of nanoparticles with alanine and glutathione can potentially be exploited to deliver drugs, even biopharmacons, across the BBB and into multiple cell types in the brain.

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