scholarly journals Role of SNAREs in Neurodegenerative Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 991
Author(s):  
Azzurra Margiotta
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Vesicle Fusion ◽  
Snare Complex ◽  
Snare Proteins ◽  
Vesicle Recycling ◽  
Brain Functions ◽  
Progressive Degeneration ◽  
Altered Regulation

Neurodegenerative diseases are pathologies of the central and peripheral nervous systems characterized by loss of brain functions and problems in movement which occur due to the slow and progressive degeneration of cellular elements. Several neurodegenerative diseases are known such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis and many studies on the molecular mechanisms underlying these pathologies have been conducted. Altered functions of some key proteins and the presence of intraneuronal aggregates have been identified as responsible for the development of the diseases. Interestingly, the formation of the SNARE complex has been discovered to be fundamental for vesicle fusion, vesicle recycling and neurotransmitter release. Indeed, inhibition of the formation of the SNARE complex, defects in the SNARE-dependent exocytosis and altered regulation of SNARE-mediated vesicle fusion have been associated with neurodegeneration. In this review, the biological aspects of neurodegenerative diseases and the role of SNARE proteins in relation to the onset of these pathologies are described.

scholarly journals The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 435 ◽  
Author(s):  
Anna Winiarska-Mieczan ◽  
Ewa Baranowska-Wójcik ◽  
Małgorzata Kwiecień ◽  
Eugeniusz R. Grela ◽  
Dominik Szwajgier ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Negative Impact ◽  
Functional Disorders ◽  
Brain Functions ◽  
Diet Supplements ◽  
The Impact ◽  
The Brain ◽  
All Diseases

Neurodegenerative diseases are progressive diseases of the nervous system that lead to neuron loss or functional disorders. Neurodegenerative diseases require long-term, sometimes life-long pharmacological treatment, which increases the risk of adverse effects and a negative impact of pharmaceuticals on the patients’ general condition. One of the main problems related to the treatment of this type of condition is the limited ability to deliver drugs to the brain due to their poor solubility, low bioavailability, and the effects of the blood-brain barrier. Given the above, one of the main objectives of contemporary scientific research focuses on the prevention of neurodegenerative diseases. As disorders related to the competence of the antioxidative system are a marker in all diseases of this type, the primary prophylactics should entail the use of exogenous antioxidants, particularly ones that can be used over extended periods, regardless of the patient’s age, and that are easily available, e.g., as part of a diet or as diet supplements. The paper analyzes the significance of the oxidoreductive balance in the pathogenesis of neurodegenerative diseases. Based on information published globally in the last 10 years, an analysis is also provided with regard to the impact of exogenous antioxidants on brain functions with respect to the prevention of this type of diseases.

scholarly journals Reconciling the regulatory role of Munc18 proteins in SNARE-complex assembly

IUCrJ ◽  
2014 ◽  
Vol 1 (6) ◽  
pp. 505-513 ◽  
Author(s):  
Asma Rehman ◽  
Julia K. Archbold ◽  
Shu-Hong Hu ◽  
Suzanne J. Norwood ◽  
Brett M. Collins ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Transmembrane Domain ◽  
Blood Glucose Control ◽  
Vital Role ◽  
Snare Complex ◽  
Snare Proteins ◽  
Regulatory Role ◽  
Sm Proteins ◽  
Protein Receptor

Membrane fusion is essential for human health, playing a vital role in processes as diverse as neurotransmission and blood glucose control. Two protein families are key: (1) the Sec1p/Munc18 (SM) and (2) the solubleN-ethylmaleimide-sensitive attachment protein receptor (SNARE) proteins. Whilst the essential nature of these proteins is irrefutable, their exact regulatory roles in membrane fusion remain controversial. In particular, whether SM proteins promote and/or inhibit the SNARE-complex formation required for membrane fusion is not resolved. Crystal structures of SM proteins alone and in complex with their cognate SNARE proteins have provided some insight, however, these structures lack the transmembrane spanning regions of the SNARE proteins and may not accurately reflect the native state. Here, we review the literature surrounding the regulatory role of mammalian Munc18 SM proteins required for exocytosis in eukaryotes. Our analysis suggests that the conflicting roles reported for these SM proteins may reflect differences in experimental design. SNARE proteins appear to require C-terminal immobilization or anchoring, for example through a transmembrane domain, to form a functional fusion complex in the presence of Munc18 proteins.

scholarly journals The role of cellular development and cell death in neurochemical organization and integrative brain functions: Normal and pathological

2004 ◽  
Vol 57 (3-4) ◽  
pp. 120-124 ◽  
Author(s):  
Vladimir Sherstnev
Keyword(s):  
Experimental Study ◽  
Learning And Memory ◽  
Molecular Mechanisms ◽  
Prognostic Markers ◽  
Brain Functions ◽  
System A ◽  
Cellular Development ◽  
Mechanisms Of Development ◽  
Apoptotic Factors

In terms of systemic aspects of common molecular mechanisms of development, important part of which is the process of cellular death and integrative activity of nervous system, a omplex clinical-experimental study of effects of various neurotrophic and apoptotic factors (proteins S100b, HLDF, brain lectins CSL and R1) on learning and memory and ishemic stroke was performed. Data concerning specific and heterochronic participation of these factors in neurochemical mechanisms of learning and memory in mechanisms of ishemic stroke formation were established. Changes of examined factors and their antibodies as well as the dynamics of changes in sera and cerebro spinal fluid can be considered as prognostic markers of ischemic stroke and efficiency of therapy.

Role of medicinal plants against neurodegenerative diseases

2021 ◽  
Vol 22 ◽  
Author(s):  
Ritika Luthra ◽  
Arpita Roy
Keyword(s):  
Medicinal Plants ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Inflammatory Responses ◽  
Vital Role ◽  
Significant Loss ◽  
Therapeutic Interventions ◽  
Inflammatory Stress

: Diseases with a significant loss of neurons, structurally and functionally are termed as neurodegenerative diseases. Due to the present therapeutic interventions and progressive nature of diseases, a variety of side effects have risen up, thus leading the patients to go for an alternative medication. The role of medicinal plants in such cases has been beneficial because of their exhibition via different cellular and molecular mechanisms. Alleviation in inflammatory responses, suppression of the functionary aspect of pro-inflammatory cytokines like a tumor, improvement in antioxidative properties is among few neuroprotective mechanisms of traditional plants. Variation in transcription and transduction pathways play a vital role in the preventive measures of plants in such diseases. Neurodegenerative diseases are generally caused by depletion of proteins, oxidative and inflammatory stress, environmental changes and so on, with aging being the most important cause. Natural compounds can be used in order to treat neurodegenerative diseases Medicinal plants such as Ginseng, Withania somnifera, Bacopa monnieri, Ginkgo biloba, etc. are some of the medicinal plants for prevention of neurological symptoms. This review deals with the use of different medicinal plants for the prevention of neurodegenerative diseases.

scholarly journals Postsynaptic regulation of synaptic plasticity by synaptotagmin 4 requires both C2 domains

2009 ◽  
Vol 187 (2) ◽  
pp. 295-310 ◽  
Author(s):  
Cynthia F. Barber ◽  
Ramon A. Jorquera ◽  
Jan E. Melom ◽  
J. Troy Littleton
Keyword(s):  
Synaptic Plasticity ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Neuromuscular Junctions ◽  
Vesicle Fusion ◽  
Synaptic Growth ◽  
Synaptotagmin 1 ◽  
Presynaptic Vesicle ◽  
Activity Dependent

Ca2+ influx into synaptic compartments during activity is a key mediator of neuronal plasticity. Although the role of presynaptic Ca2+ in triggering vesicle fusion though the Ca2+ sensor synaptotagmin 1 (Syt 1) is established, molecular mechanisms that underlie responses to postsynaptic Ca2+ influx remain unclear. In this study, we demonstrate that fusion-competent Syt 4 vesicles localize postsynaptically at both neuromuscular junctions (NMJs) and central nervous system synapses in Drosophila melanogaster. Syt 4 messenger RNA and protein expression are strongly regulated by neuronal activity, whereas altered levels of postsynaptic Syt 4 modify synaptic growth and presynaptic release properties. Syt 4 is required for known forms of activity-dependent structural plasticity at NMJs. Synaptic proliferation and retrograde signaling mediated by Syt 4 requires functional C2A and C2B Ca2+–binding sites, as well as serine 284, an evolutionarily conserved substitution for a key Ca2+-binding aspartic acid found in other synaptotagmins. These data suggest that Syt 4 regulates activity-dependent release of postsynaptic retrograde signals that promote synaptic plasticity, similar to the role of Syt 1 as a Ca2+ sensor for presynaptic vesicle fusion.

scholarly journals How Could SNARE Proteins Open a Fusion Pore?

Physiology ◽  
2014 ◽  
Vol 29 (4) ◽  
pp. 278-285 ◽  
Author(s):  
Qinghua Fang ◽  
Manfred Lindau
Keyword(s):  
Conformational Change ◽  
Pore Formation ◽  
Vesicle Fusion ◽  
Neurosecretory Cells ◽  
Snare Complex ◽  
Snare Proteins ◽  
Fusion Pore ◽  
Receptor Complex ◽  
Attachment Protein ◽  
Protein Receptor

The SNARE (Soluble NSF Attachment protein REceptor) complex, which in mammalian neurosecretory cells is composed of the proteins synaptobrevin 2 (also called VAMP2), syntaxin, and SNAP-25, plays a key role in vesicle fusion. In this review, we discuss the hypothesis that, in neurosecretory cells, fusion pore formation is directly accomplished by a conformational change in the SNARE complex via movement of the transmembrane domains.

scholarly journals Differential inhibition by botulinum neurotoxin A of cotransmitters released from autonomic vasodilator neurons

2001 ◽  
Vol 281 (5) ◽  
pp. H2124-H2132 ◽  
Author(s):  
Judy L. Morris ◽  
Phillip Jobling ◽  
Ian L. Gibbins
Keyword(s):  
Botulinum Neurotoxin ◽  
Snare Complex ◽  
Snare Proteins ◽  
Botulinum Neurotoxin A ◽  
Uterine Arteries ◽  
Synaptic Vesicle Exocytosis ◽  
Protein Receptor ◽  
Autonomic Neurons ◽  
Vesicle Exocytosis

The role of the soluble NSF attachment protein receptor (SNARE) protein complex in release of multiple cotransmitters from autonomic vasodilator neurons was examined in isolated segments of guinea pig uterine arteries treated with botulinum neurotoxin A (BoNTA; 50 nM). Western blotting of protein extracts from uterine arteries demonstrated partial cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25) to a NH2-terminal fragment of ∼24 kDa by BoNTA. BoNTA reduced the amplitude (by 70–80%) of isometric contractions of arteries in response to repeated electrical stimulation of sympathetic axons at 1 or 10 Hz. The amplitude of neurogenic relaxations mediated by neuronal nitric oxide (NO) was not affected by BoNTA, whereas the duration of peptide-mediated neurogenic relaxations to stimulation at 10 Hz was reduced (67% reduction in integrated responses). In contrast, presynaptic cholinergic inhibition of neurogenic relaxations was abolished by BoNTA. These results demonstrate that the SNARE complex has differential involvement in release of cotransmitters from the same autonomic neurons: NO release is not dependant on synaptic vesicle exocytosis, acetylcholine release from small vesicles is highly dependant on the SNARE complex, and neuropeptide release from large vesicles involves SNARE proteins that may interact differently with regulatory factors such as calcium.

scholarly journals Redox Imbalance and Viral Infections in Neurodegenerative Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Dolores Limongi ◽  
Sara Baldelli
Keyword(s):  
Neurodegenerative Diseases ◽  
Viral Infection ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Second Messengers ◽  
Chronic Viral Infections ◽  
Ros Accumulation ◽  
Simplex Virus

Reactive oxygen species (ROS) are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS).

scholarly journals Mitophagy Regulates Neurodegenerative Diseases

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1876
Author(s):  
Xufeng Cen ◽  
Manke Zhang ◽  
Mengxin Zhou ◽  
Lingzhi Ye ◽  
Hongguang Xia
Keyword(s):  
Neurodegenerative Diseases ◽  
Signaling Pathways ◽  
Neurodegenerative Disorders ◽  
Essential Role ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Treatment Strategies ◽  
Metabolic Process ◽  
Recent Advances

Mitochondria play an essential role in supplying energy for the health and survival of neurons. Mitophagy is a metabolic process that removes dysfunctional or redundant mitochondria. This process preserves mitochondrial health. However, defective mitophagy triggers the accumulation of damaged mitochondria, causing major neurodegenerative disorders. This review introduces molecular mechanisms and signaling pathways behind mitophagy regulation. Furthermore, we focus on the recent advances in understanding the potential role of mitophagy in the pathogenesis of major neurodegenerative diseases (Parkinson’s, Alzheimer’s, Huntington’s, etc.) and aging. The findings will help identify the potential interventions of mitophagy regulation and treatment strategies of neurodegenerative diseases.

scholarly journals Role of Network Science in the Study of Anesthetic State Transitions

2018 ◽  
Vol 129 (5) ◽  
pp. 1029-1044 ◽  
Author(s):  
UnCheol Lee ◽  
George A. Mashour
Keyword(s):  
General Anesthesia ◽  
Molecular Mechanisms ◽  
Network Science ◽  
State Transitions ◽  
General Anesthetics ◽  
Network Efficiency ◽  
Cortical Dynamics ◽  
Brain Functions ◽  
Complex Interactions

Abstract The heterogeneity of molecular mechanisms, target neural circuits, and neurophysiologic effects of general anesthetics makes it difficult to develop a reliable and drug-invariant index of general anesthesia. No single brain region or mechanism has been identified as the neural correlate of consciousness, suggesting that consciousness might emerge through complex interactions of spatially and temporally distributed brain functions. The goal of this review article is to introduce the basic concepts of networks and explain why the application of network science to general anesthesia could be a pathway to discover a fundamental mechanism of anesthetic-induced unconsciousness. This article reviews data suggesting that reduced network efficiency, constrained network repertoires, and changes in cortical dynamics create inhospitable conditions for information processing and transfer, which lead to unconsciousness. This review proposes that network science is not just a useful tool but a necessary theoretical framework and method to uncover common principles of anesthetic-induced unconsciousness.

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