scholarly journals Astrocytes and their Phenomenal Possibilities in the Treatment of Various Neurodegenerative Disorders: An Overview

2021 ◽  
pp. 60-68
Author(s):  
Alina Yuryevna Maslova ◽  
Kheda Lechaevna Bazaeva ◽  
Zaira Arazovna Abdullaeva ◽  
Shuainat Omarovna Khazamova ◽  
Karina Akhmedovna Zeusheva ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Brain Injuries ◽  
Neurological Diseases ◽  
External Environment ◽  
Close Attention ◽  
Rate Of Development ◽  
Pharmacological Modulation ◽  
Cerebral Neurons ◽  
Cns Pathology ◽  
The Brain

At present, research in the field of the brain does not cease to surprise us with new facts and discoveries that no one could have suspected about 30 years ago. But it was at the time when it became clear that the cerebral neurons are not the only cells that can respond to changes in the external environment. A real scientific boom began to study a heterogeneous group called glia. And scientists are paying close attention to the largest of them – astrocytes. Understanding the importance of astrocytes in the mechanisms of repair and damage to brain cells in various forms of CNS pathology determines the possibility of targeted search for drugs that affect the rate of development of reactive astrogliosis in response to various brain injuries. At the same time, pharmacological modulation of activated astrocytes and other components of glia can be an integral part of the therapy of neurological diseases.

scholarly journals Human Monocytes Plasticity in Neurodegeneration

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 717
Author(s):  
Ilenia Savinetti ◽  
Angela Papagna ◽  
Maria Foti
Keyword(s):  
Neurodegenerative Disorders ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Surface Marker ◽  
First Line ◽  
Surface Marker Expression ◽  
Physiological Properties ◽  
Attractive Therapeutic Target ◽  
The Brain ◽  
Lateral Sclerosis

Monocytes play a crucial role in immunity and tissue homeostasis. They constitute the first line of defense during the inflammatory process, playing a role in the pathogenesis and progression of diseases, making them an attractive therapeutic target. They are heterogeneous in morphology and surface marker expression, which suggest different molecular and physiological properties. Recent evidences have demonstrated their ability to enter the brain, and, as a consequence, their hypothetical role in different neurodegenerative diseases. In this review, we will discuss the current knowledge about the correlation between monocyte dysregulation in the brain and/or in the periphery and neurological diseases in humans. Here we will focus on the most common neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis.

scholarly journals ASTROCYTES AND THEIR ROLE IN THE PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM

2019 ◽  
Vol 21 (1) ◽  
pp. 46-53
Author(s):  
L. R. Gorbacheva ◽  
I. A. Pomytkin ◽  
A. M. Surin ◽  
E. A. Abramov ◽  
Vsevolod G. Pinelis
Keyword(s):  
Glial Cells ◽  
Brain Injuries ◽  
Negative Impact ◽  
Neurological Diseases ◽  
Clinical Neurology ◽  
Actual Problem ◽  
Functional Changes ◽  
Repair Mechanisms ◽  
Progressive Neurodegeneration ◽  
The Brain

Determination of the structural-functional significance of astrocytes in the physiology and pathology of the CNS is an actual problem of modern neuroscience and clinical neurology. Astrocytes are glial cells of the brain, constitute the substance of the brain, support neurons and separate them with their bodies into compartments. They participate in the immune response of the brain, they are able to maintain the chronic inflammation and progressive neurodegeneration due to overexpression of cytokines, growth factors, and chemokines. This review discusses the key features of astrogliosis as complex of molecular, cellular and functional changes of astrocytes in the response to various brain injuries. Reactive astrogliosis is critical for regeneration and remodeling of neural networks after the injury and ischemia and can have both positive and negative impact. The overexpression of S100b protein is an index of the astrocyte activation, which is characteristic for glial cells as this protein is located mainly in astrocytes. In cerebral ischemia, traumatic brain injury or neurodegenerative diseases there is the modulation of astrogliosis, aimed at the provision of repair mechanisms of the damaged parts of the brain that determines search capabilities of the new means of pharmacological correction of activated astrocytes and other glial components for the treatment of neurological diseases.

scholarly journals Prognostic Value and Therapeutic Potential of Brain-Derived Neurotrophic Factor (BDNF) in Brain Injuries (Review)

2019 ◽  
Vol 15 (1) ◽  
pp. 70-86 ◽  
Author(s):  
I. V. Ostrova ◽  
N. V. Golubeva ◽  
A. N. Kuzovlev ◽  
A. M. Golubev
Keyword(s):  
Neurotrophic Factor ◽  
Brain Injuries ◽  
Therapeutic Potential ◽  
Neuronal Survival ◽  
Brain Derived Neurotrophic Factor ◽  
Brain Dysfunction ◽  
Common Mechanism ◽  
Close Attention ◽  
System Functioning ◽  
The Brain

Neurotrophins are proteins that play an important role in the nervous system functioning by regulating cell proliferation, differentiation, processes of neuronal survival and death, and by participating in the mechanisms of neuronal plasticity. The brain-derived neurotrophic factor (BDNF) is one of the most well-described representatives of the neurotrophin family, which has received close attention over recent years. It is considered one of the key mediators of neuronal survival and recovery, and a drop of the BDNF level is considered a common mechanism underlying the development of various neurodegenerative diseases. The review discusses changes in BDNF levels in ischemic and traumatic brain damage, the prospects of its use in the clinical practice as a marker of brain dysfunction, as well as the possibility of its use for the treatment of post-ischemic encephalopathies.

Neuroregenerative strategies in the brain: emerging significance of bone morphogenetic protein 7 (BMP7)

2008 ◽  
Vol 86 (5) ◽  
pp. 361-369 ◽  
Author(s):  
Mahmud Bani-Yaghoub ◽  
Roger G. Tremblay ◽  
Abdellah Ajji ◽  
Munyao Nzau ◽  
Sandhya Gangaraju ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Brain Injuries ◽  
Neurological Diseases ◽  
Neuronal Loss ◽  
The Novel ◽  
Brain Repair ◽  
Bone Morphogenetic Protein 7 ◽  
Morphogenetic Protein ◽  
Cognitive Problems ◽  
The Brain

Every year thousands of people suffer from brain injuries and stroke, and develop motor, sensory, and cognitive problems as a result of neuronal loss in the brain. Unfortunately, the damaged brain has a limited ability to enact repair and current modes of treatment are not sufficient to offset the damage. An extensive list of growth factors, neurotrophic factors, cytokines, and drugs has been explored as potential therapies. However, only a limited number of them may actually have the potential to effectively offset the brain injury or stroke-related problems. One of the treatments considered for future brain repair is bone morphogenetic protein 7 (BMP7), a factor currently used in patients to treat non-neurological diseases. The clinical application of BMP7 is based on its neuroprotective role in stroke animal models. This paper reviews the current approaches considered for brain repair and discusses the novel convergent strategies by which BMP7 potentially can induce neuroregeneration.

scholarly journals Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant

2020 ◽  
Vol 21 (15) ◽  
pp. 5271
Author(s):  
Rachida Guennoun
Keyword(s):  
Brain Injuries ◽  
Neurological Diseases ◽  
Progesterone Receptors ◽  
Experimental Models ◽  
Current Data ◽  
Neuroprotective Effects ◽  
Specific Receptors ◽  
Multiple Signaling ◽  
The Brain

Progesterone has a broad spectrum of actions in the brain. Among these, the neuroprotective effects are well documented. Progesterone neural effects are mediated by multiple signaling pathways involving binding to specific receptors (intracellular progesterone receptors (PR); membrane-associated progesterone receptor membrane component 1 (PGRMC1); and membrane progesterone receptors (mPRs)) and local bioconversion to 3α,5α-tetrahydroprogesterone (3α,5α-THPROG), which modulates GABAA receptors. This brief review aims to give an overview of the synthesis, metabolism, neuroprotective effects, and mechanism of action of progesterone in the rodent and human brain. First, we succinctly describe the biosynthetic pathways and the expression of enzymes and receptors of progesterone; as well as the changes observed after brain injuries and in neurological diseases. Then, we summarize current data on the differential fluctuations in brain levels of progesterone and its neuroactive metabolites according to sex, age, and neuropathological conditions. The third part is devoted to the neuroprotective effects of progesterone and 3α,5α-THPROG in different experimental models, with a focus on traumatic brain injury and stroke. Finally, we highlight the key role of the classical progesterone receptors (PR) in mediating the neuroprotective effects of progesterone after stroke.

Brain Drug Delivery: Overcoming the Blood-brain Barrier to Treat Tauopathies

2020 ◽  
Vol 26 (13) ◽  
pp. 1448-1465 ◽  
Author(s):  
Jozef Hanes ◽  
Eva Dobakova ◽  
Petra Majerova
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Neurodegenerative Disorders ◽  
Brain Barrier ◽  
Neuronal Function ◽  
Brain Drug Delivery ◽  
Naturally Occurring ◽  
Blood Brain ◽  
Traditional Approaches ◽  
The Brain

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.

Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

2019 ◽  
Vol 18 (8) ◽  
pp. 581-597 ◽  
Author(s):  
Ambreen Fatima ◽  
Yasir Hasan Siddique
Keyword(s):  
Medicinal Plants ◽  
Mechanism Of Action ◽  
Neurodegenerative Disorders ◽  
Treatment Strategies ◽  
Dietary Supplementation ◽  
Plant Polyphenols ◽  
Promising Candidate ◽  
Naturally Occurring ◽  
The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

Methyl jasmonate delays the latency to anoxic convulsions by normalizing the brain levels of oxidative stress biomarkers and serum corticosterone contents in mice with repeated anoxic stress

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Abayomi Ololade Adelaja ◽  
Oluwafemi Gabriel Oluwole ◽  
Oritoke Modupe. Aluko ◽  
Solomon Umukoro
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Methyl Jasmonate ◽  
Brain Injuries ◽  
Antioxidant Property ◽  
Oxidative Stress Biomarkers ◽  
Serum Corticosterone ◽  
Stress Agent ◽  
Cellular Antioxidants ◽  
The Brain

AbstractObjectivesRepeated exposure to anoxic stress damages the brain through cortisol-mediated increases in oxidative stress and cellular-antioxidants depletion. Thus, compounds with antioxidant property might confer protection against anoxic stress-induced brain injuries. In this study, we further examined the protective effect of methyl jasmonate (MJ), a potent anti-stress agent against anoxic stress-induced convulsions in mice.MethodsThirty-six male Swiss mice randomized into six groups (n=6) were given MJ (25, 50 and 100 mg/kg, i.p.) or vehicle (10 mL/kg, i.p.) 30 min before 15 min daily exposure to anoxic stress for 7 days. The latency(s) to anoxic convulsion was recorded on day 7. The blood glucose and serum corticosterone levels were measured afterwards. The brains were also processed for the determination of malondialdehyde, nitrite, and glutathione levels.ResultsMethyl jasmonate (MJ) delayed the latency to anoxic convulsion and reduced the blood glucose and serum corticosterone levels. The increased malondialdehyde and nitrite contents accompanied by decreased glutathione concentrations in mice with anoxic stress were significantly attenuated by MJ.ConclusionsThese findings further showed that MJ possesses anti-stress property via mechanisms relating to the reduction of serum contents of corticosterone and normalization of brain biomarker levels of oxidative stress in mice with anoxic stress.

scholarly journals Molecular mechanisms of metabotropic GABAB receptor function

2021 ◽  
Vol 7 (22) ◽  
pp. eabg3362
Author(s):  
Hamidreza Shaye ◽  
Benjamin Stauch ◽  
Cornelius Gati ◽  
Vadim Cherezov
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Gabab Receptor ◽  
Neurological Diseases ◽  
Activation Mechanism ◽  
Allosteric Modulators ◽  
Inhibitory Neurotransmitter ◽  
Therapeutic Drugs ◽  
G Protein Coupled ◽  
The Brain

Metabotropic γ-aminobutyric acid G protein–coupled receptors (GABAB) represent one of the two main types of inhibitory neurotransmitter receptors in the brain. These receptors act both pre- and postsynaptically by modulating the transmission of neuronal signals and are involved in a range of neurological diseases, from alcohol addiction to epilepsy. A series of recent cryo-EM studies revealed critical details of the activation mechanism of GABAB. Structures are now available for the receptor bound to ligands with different modes of action, including antagonists, agonists, and positive allosteric modulators, and captured in different conformational states from the inactive apo to the fully active state bound to a G protein. These discoveries provide comprehensive insights into the activation of the GABAB receptor, which not only broaden our understanding of its structure, pharmacology, and physiological effects but also will ultimately facilitate the discovery of new therapeutic drugs and neuromodulators.

scholarly journals Molecular mechanisms of cell death in neurological diseases

2021 ◽  
Author(s):  
Diane Moujalled ◽  
Andreas Strasser ◽  
Jeffrey R. Liddell
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Response To Therapy ◽  
Signalling Cascades ◽  
The Brain

AbstractTightly orchestrated programmed cell death (PCD) signalling events occur during normal neuronal development in a spatially and temporally restricted manner to establish the neural architecture and shaping the CNS. Abnormalities in PCD signalling cascades, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and cell death associated with autophagy as well as in unprogrammed necrosis can be observed in the pathogenesis of various neurological diseases. These cell deaths can be activated in response to various forms of cellular stress (exerted by intracellular or extracellular stimuli) and inflammatory processes. Aberrant activation of PCD pathways is a common feature in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, resulting in unwanted loss of neuronal cells and function. Conversely, inactivation of PCD is thought to contribute to the development of brain cancers and to impact their response to therapy. For many neurodegenerative diseases and brain cancers current treatment strategies have only modest effect, engendering the need for investigations into the origins of these diseases. With many diseases of the brain displaying aberrations in PCD pathways, it appears that agents that can either inhibit or induce PCD may be critical components of future therapeutic strategies. The development of such therapies will have to be guided by preclinical studies in animal models that faithfully mimic the human disease. In this review, we briefly describe PCD and unprogrammed cell death processes and the roles they play in contributing to neurodegenerative diseases or tumorigenesis in the brain. We also discuss the interplay between distinct cell death signalling cascades and disease pathogenesis and describe pharmacological agents targeting key players in the cell death signalling pathways that have progressed through to clinical trials.

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