scholarly journals O-GlcNAcylation in health and neurodegenerative diseases

2021 ◽  
Author(s):  
Byeong Eun Lee ◽  
Pann-Ghill Suh ◽  
Jae-Ick Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Posttranslational Modification ◽  
Protein Modification ◽  
Molecular Mechanisms ◽  
The Body ◽  
Neuroprotective Effects ◽  
Functional Roles ◽  
Cellular Pathways ◽  
Neuronal Functions ◽  
The Brain

AbstractO-GlcNAcylation is a posttranslational modification that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of many proteins. This protein modification interacts with key cellular pathways involved in transcription, translation, and proteostasis. Although ubiquitous throughout the body, O-GlcNAc is particularly abundant in the brain, and various proteins commonly found at synapses are O-GlcNAcylated. Recent studies have demonstrated that the modulation of O-GlcNAc in the brain alters synaptic and neuronal functions. Furthermore, altered brain O-GlcNAcylation is associated with either the etiology or pathology of numerous neurodegenerative diseases, while the manipulation of O-GlcNAc exerts neuroprotective effects against these diseases. Although the detailed molecular mechanisms underlying the functional roles of O-GlcNAcylation in the brain remain unclear, O-GlcNAcylation is critical for regulating diverse neural functions, and its levels change during normal and pathological aging. In this review, we will highlight the functional importance of O-GlcNAcylation in the brain and neurodegenerative diseases.

scholarly journals Ingredients for Functional Drinks in Neurodegenerative Diseases: A Review

2009 ◽  
Vol 4 (5) ◽  
pp. 1934578X0900400
Author(s):  
Pilar Zafrilla ◽  
Juana M Morulas ◽  
José M. Rubio-Perez ◽  
Emma Cantos Villar
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Clinical Evidence ◽  
The Body ◽  
Neuroprotective Effects ◽  
Antioxidant Agents ◽  
Rate Of Progression ◽  
The Brain

Several studies have indicated that oxidative stress is a major risk factor for the initiation and progression of neurological disorders like Parkinson's disease (PD) and Alzheimer's (AD). Therefore, reducing oxidative stress appears to be a rational choice for the prevention and reduction in the rate of progression of these neurological disorders. The brain utilizes about 25% of respired oxygen even though it represents only 5% of the body weight. Free radicals are generated during the normal intake of oxygen, during infection, and during normal oxidative metabolism of certain substrates. Although experimental data are consistent in demonstrating the neuroprotective effects of antioxidants in vitro and in animal models, the clinical evidence that antioxidant agents may prevent or slow the course of these diseases is still relatively unsatisfactory, and insufficient to strongly modify clinical practice. In this paper, natural possible substances that could be added to a beverage to prevent or decrease the developing of neurodegenerative diseases are reviewed.

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.

scholarly journals Ganglioside GM1 Targets Astrocytes to Stimulate Cerebral Energy Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Charles Finsterwald ◽  
Sara Dias ◽  
Pierre J. Magistretti ◽  
Sylvain Lengacher
Keyword(s):  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Brain Diseases ◽  
Mitochondrial Activity ◽  
Ganglioside Gm1 ◽  
Neuroprotective Effects ◽  
Wide Range ◽  
Cord Injury ◽  
Clinical Benefits ◽  
The Brain

Gangliosides are major constituents of the plasma membrane and are known to promote a number of physiological actions in the brain, including synaptic plasticity and neuroprotection. In particular, the ganglioside GM1 was found to have a wide range of preclinical and clinical benefits in brain diseases such as spinal cord injury, Huntington’s disease and Parkinson’s disease. However, little is known about the underlying cellular and molecular mechanisms of GM1 in the brain. In the present study, we show that GM1 exerts its actions through the promotion of glycolysis in astrocytes, which leads to glucose uptake and lactate release by these cells. In astrocytes, GM1 stimulates the expression of several genes involved in the regulation of glucose metabolism. GM1 also enhances neuronal mitochondrial activity and triggers the expression of neuroprotection genes when neurons are cultured in the presence of astrocytes. Finally, GM1 leads to a neuroprotective effect in astrocyte-neuron co-culture. Together, these data identify a previously unrecognized mechanism mediated by astrocytes by which GM1 exerts its metabolic and neuroprotective effects.

scholarly journals Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection

2020 ◽  
Vol 21 (7) ◽  
pp. 2501 ◽  
Author(s):  
Thomas Nury ◽  
Gérard Lizard ◽  
Anne Vejux
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Cell Death ◽  
Neurodegenerative Diseases ◽  
The Body ◽  
Protein Accumulation ◽  
Common Features ◽  
Apoptosis And Inflammation ◽  
The Brain ◽  
And Oxidative Stress

Neurodegenerative diseases, particularly Parkinson’s and Alzheimer’s, have common features: protein accumulation, cell death with mitochondrial involvement and oxidative stress. Patients are treated to cure the symptoms, but the treatments do not target the causes; so, the disease is not stopped. It is interesting to look at the side of nutrition which could help prevent the first signs of the disease or slow its progression in addition to existing therapeutic strategies. Lipids, whether in the form of vegetable or animal oils or in the form of fatty acids, could be incorporated into diets with the aim of preventing neurodegenerative diseases. These different lipids can inhibit the cytotoxicity induced during the pathology, whether at the level of mitochondria, oxidative stress or apoptosis and inflammation. The conclusions of the various studies cited are oriented towards the preventive use of oils or fatty acids. The future of these lipids that can be used in therapy/prevention will undoubtedly involve a better delivery to the body and to the brain by utilizing lipid encapsulation.

scholarly journals Brain manganese and the balance between essential roles and neurotoxicity

2020 ◽  
Vol 295 (19) ◽  
pp. 6312-6329 ◽  
Author(s):  
Rekha C. Balachandran ◽  
Somshuvra Mukhopadhyay ◽  
Danielle McBride ◽  
Jennifer Veevers ◽  
Fiona E. Harrison ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Normal Development ◽  
The Body ◽  
Neurological Dysfunction ◽  
Cellular Transport ◽  
Brain Health ◽  
Biochemical Mechanisms ◽  
Molecular And Biochemical Mechanisms ◽  
Neuronal Physiology ◽  
The Brain

Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity.

scholarly journals Regulatory Roles of Bone in Neurodegenerative Diseases

2020 ◽  
Vol 12 ◽  
Author(s):  
Zhengran Yu ◽  
Zemin Ling ◽  
Lin Lu ◽  
Jin Zhao ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
The Elderly ◽  
Lymphoid Organ ◽  
The Body ◽  
Hematopoietic Stem ◽  
Brain Functions ◽  
And Function ◽  
The Impact ◽  
The Brain

Osteoporosis and neurodegenerative diseases are two kinds of common disorders of the elderly, which often co-occur. Previous studies have shown the skeletal and central nervous systems are closely related to pathophysiology. As the main structural scaffold of the body, the bone is also a reservoir for stem cells, a primary lymphoid organ, and an important endocrine organ. It can interact with the brain through various bone-derived cells, mostly the mesenchymal and hematopoietic stem cells (HSCs). The bone marrow is also a place for generating immune cells, which could greatly influence brain functions. Finally, the proteins secreted by bones (osteokines) also play important roles in the growth and function of the brain. This article reviews the latest research studying the impact of bone-derived cells, bone-controlled immune system, and bone-secreted proteins on the brain, and evaluates how these factors are implicated in the progress of neurodegenerative diseases and their potential use in the diagnosis and treatment of these diseases.

scholarly journals Cerebral sterile inflammation in neurodegenerative diseases

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Kento Otani ◽  
Takashi Shichita
Keyword(s):  
Immune Responses ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Agents ◽  
Sterile Inflammation ◽  
Cellular Damage ◽  
Cellular Mechanisms ◽  
Abnormal Accumulation ◽  
The Brain ◽  
Lateral Sclerosis

AbstractTherapeutic strategies for regulating neuroinflammation are expected in the development of novel therapeutic agents to prevent the progression of central nervous system (CNS) pathologies. An understanding of the detailed molecular and cellular mechanisms of neuroinflammation in each CNS disease is necessary for the development of therapeutics. Since the brain is a sterile organ, neuroinflammation in Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) is triggered by cerebral cellular damage or the abnormal accumulation of inflammatogenic molecules in CNS tissue through the activation of innate and acquired immunity. Inflammation and CNS pathologies worsen each other through various cellular and molecular mechanisms, such as oxidative stress or the accumulation of inflammatogenic molecules induced in the damaged CNS tissue. In this review, we summarize the recent evidence regarding sterile immune responses in neurodegenerative diseases.

scholarly journals Molekulare Kontrolle der Stabilität und Plastizität von Synapsen

BIOspektrum ◽  
2021 ◽  
Vol 27 (6) ◽  
pp. 588-590
Author(s):  
Zeeshan Mushtaq ◽  
Jan Pielage
Keyword(s):  
Nervous System ◽  
Synaptic Plasticity ◽  
Neurodegenerative Diseases ◽  
Information Flow ◽  
Molecular Mechanisms ◽  
Synaptic Connectivity ◽  
Genetic Mutations ◽  
Neuronal Circuits ◽  
The Brain

AbstractThe precise regulation of synaptic connectivity is essential for the processing of information in the brain. Any aberrant loss of synaptic connectivity due to genetic mutations will disrupt information flow in the nervous system and may represent the underlying cause of psychiatric or neurodegenerative diseases. Therefore, identification of the molecular mechanisms controlling synaptic plasticity and maintenance is essential for our understanding of neuronal circuits in development and disease.

scholarly journals Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity

2020 ◽  
Author(s):  
Laura Casares ◽  
Juan Diego Unciti ◽  
Maria Eugenia Prados ◽  
Diego Caprioglio ◽  
Maureen Higgins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
The Brain

ABSTRACTOxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, Huntington’s and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington’s disease, setting the basis for further developments in vivo.

scholarly journals Microglia Specific Drug Targeting Using Natural Products for the Regulation of Redox Imbalance in Neurodegeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Shashank Kumar Maurya ◽  
Neetu Bhattacharya ◽  
Suman Mishra ◽  
Amit Bhattacharya ◽  
Pratibha Banerjee ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Neuroprotective Effect ◽  
Inhibitory Effect ◽  
Dual Function ◽  
Redox Imbalance ◽  
The Brain

Microglia, a type of innate immune cell of the brain, regulates neurogenesis, immunological surveillance, redox imbalance, cognitive and behavioral changes under normal and pathological conditions like Alzheimer’s, Parkinson’s, Multiple sclerosis and traumatic brain injury. Microglia produces a wide variety of cytokines to maintain homeostasis. It also participates in synaptic pruning and regulation of neurons overproduction by phagocytosis of neural precursor cells. The phenotypes of microglia are regulated by the local microenvironment of neurons and astrocytes via interaction with both soluble and membrane-bound mediators. In case of neuron degeneration as observed in acute or chronic neurodegenerative diseases, microglia gets released from the inhibitory effect of neurons and astrocytes, showing activated phenotype either of its dual function. Microglia shows neuroprotective effect by secreting growths factors to heal neurons and clears cell debris through phagocytosis in case of a moderate stimulus. But the same microglia starts releasing pro-inflammatory cytokines like TNF-α, IFN-γ, reactive oxygen species (ROS), and nitric oxide (NO), increasing neuroinflammation and redox imbalance in the brain under chronic signals. Therefore, pharmacological targeting of microglia would be a promising strategy in the regulation of neuroinflammation, redox imbalance and oxidative stress in neurodegenerative diseases. Some studies present potentials of natural products like curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane to suppress activation of microglia. These natural products have also been proposed as effective therapeutics to regulate the progression of neurodegenerative diseases. The present review article intends to explain the molecular mechanisms and functions of microglia and molecular dynamics of microglia specific genes and proteins like Iba1 and Tmem119 in neurodegeneration. The possible interventions by curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane on microglia specific protein Iba1 suggest possibility of natural products mediated regulation of microglia phenotypes and its functions to control redox imbalance and neuroinflammation in management of Alzheimer’s, Parkinson’s and Multiple Sclerosis for microglia-mediated therapeutics.

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