Functional Neuroproteomics: An imperative approach for unravelling protein implicated complexities of brain.

2021 ◽  
Vol 20 ◽  
Author(s):  
Ibraheem Husain ◽  
Wasim Ahmad ◽  
Abuzer Ali ◽  
Laiba Anwar ◽  
Sheikh Md Nuruddin ◽  
...  
Keyword(s):  
Communication Channel ◽  
Presynaptic Terminal ◽  
Brain Cells ◽  
Functional Proteomics ◽  
Single Neurons ◽  
Building Site ◽  
Physiological Conditions ◽  
Neuronal Communication ◽  
Functional Studies ◽  
Physiological Processes

: A proteome is defined as a comprehensive protein set either of an organ or an organism at a given time and under specific physiological conditions and accordingly, the study of nervous system’s proteomes is called Neuroproteomics. In the neuroproteomics process, various pieces of the nervous system are “fragmented” to understand the dynamics of each given sub-proteome in a much better way. Functional proteomics addresses the organisation of proteins into complexes, and formation of organelles from these multiprotein complexes that control various physiological processes. Current functional studies of neuroproteomics mainly talk about the synapse structure and its organisation, the major building site of the neuronal communication channel. The proteomes of synaptic vesicle, presynaptic terminal, and postsynaptic density, have been examined by various proteomics techniques. The objective of functional neuroproteomics is to solve the proteome of single neurons or astrocytes grown in cell cultures or from the primary brain cells isolated from tissues under various conditions; to identify set of proteins which characterize a specific pathogenesis; or to determine the group of proteins making up post-synaptic or pre-synaptic densities. It is very usual to try to solve a particular sub-proteome like the heatshock response proteome, or the proteome responding to inflammation. Posttranslational protein modifications alter their functions and interactions. The techniques to detect synapse phosphoproteome are available however, those for the analysis of ubiquitination and sumoylation, are under development.

Krankheit als Funktionsgestörtheit

1990 ◽  
Vol 12 (1) ◽  
Author(s):  
Markus Pawelzik
Keyword(s):  
Well Being ◽  
Modern Medicine ◽  
Alternative Conception ◽  
Critical Examination ◽  
Medical Sciences ◽  
Physiological Conditions ◽  
Medical Disease ◽  
Physiological Processes

AbstractContrary to the bio-medical sciences most philosophers of medicine regard disease as an evaluative concept. C. Boorse’s well- known naturalist attempt to conceptualize disease exclusively on the basis of physiological fact seems highly plausible at first sight, since on this Supposition it is possible to make use of the impressive explanatory knowledge of modern medicine. But critical examination of his meta- physiological notion of “disease” as subnormal functioning shows that it does not conform to licensed medical disease-judgements. Furthermore his doctrine seems unjustified since it’s empirical implementability is highly questionable. This suggests that medicine is a naturalist enterprise that is guided by evaluation. An alternative conception of disease is advanced that tries to make the ‘nexus’ of physiological fact and evaluation intelligible: Disease is (extensionally) the class of physiological processes that (actually or prospectively) undermine the physiological conditions of human well-being.

scholarly journals Systematic survey of deubiquitinase localization identifies USP21 as a regulator of centrosome- and microtubule-associated functions

2012 ◽  
Vol 23 (6) ◽  
pp. 1095-1103 ◽  
Author(s):  
Sylvie Urbé ◽  
Han Liu ◽  
Sebastian D. Hayes ◽  
Claire Heride ◽  
Daniel J. Rigden ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
A549 Cells ◽  
Binding Motif ◽  
Vitro Assay ◽  
Microtubule Binding ◽  
Functional Studies ◽  
Physiological Processes ◽  
Associated Functions ◽  
Green Fluorescent

Ubiquitination is a reversible modification that influences a broad range of physiological processes. There are approximately 90 deubiquitinases (DUBs) encoded in the human genome, of which 79 are predicted to have catalytic activity. We tagged 66 DUBs with green fluorescent protein and systematically surveyed their subcellular distribution, identifying enzymes specific to the nucleus, plasma membrane, and secretory and endocytic pathways. USP21 is unique in showing clear association with both centrosomes and microtubules. Using an in vitro assay, we show that microtubule binding is direct and identify a novel microtubule-binding motif encompassed within amino acids 59–75 of the N-terminus of USP21. Our functional studies indicate a key role for USP21 in the governance of microtubule- and centrosome-associated physiological processes: Depletion of USP21 in A549 cells compromises the reestablishment of a radial array of microtubules during recovery from cold-induced depolymerization and also reduces the probability of primary cilium formation, whereas USP21 knockdown in PC12 cells inhibits nerve growth factor–induced neurite outgrowth.

Mechanisms controlling the expression of the components of the exocytotic apparatus under physiological and pathological conditions

2006 ◽  
Vol 34 (5) ◽  
pp. 696-700 ◽  
Author(s):  
A. Abderrahmani ◽  
V. Plaisance ◽  
P. Lovis ◽  
R. Regazzi
Keyword(s):  
Diabetes Mellitus ◽  
Transcription Factors ◽  
Bioactive Compounds ◽  
Cellular Level ◽  
Physiological Conditions ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
New Perspective ◽  
Shed Light ◽  
Striking Contrast

The last decade has witnessed spectacular progress in the identification of the protein apparatus required for exocytosis of neurotransmitters, peptide hormones and other bioactive products. In striking contrast, our knowledge of the mechanisms determining the expression of the components of the secretory machinery has remained rudimentary. Since modifications in secretory functions are associated with several physiological processes and contribute to the development of human pathologies, a better knowledge of the control of the expression of the genes involved in exocytosis is urgently needed. Recent studies have led to the identification of transcription factors and other regulatory molecules such as microRNAs that modulate the cellular level of key controllers of the exocytotic process. These findings furnish a new perspective for understanding how secretory functions can adapt to normal physiological conditions and shed light on the mechanisms involved in the development of important human diseases such as diabetes mellitus characterized by defective release of bioactive compounds.

New Strategy for Controlled Release of Nitric Oxide

2012 ◽  
Vol 20 ◽  
pp. 61-67 ◽  
Author(s):  
Amedea B. Seabra ◽  
Priscyla D. Marcato ◽  
Larissa B. de Paula ◽  
Nelson Durán
Keyword(s):  
Nitric Oxide ◽  
Vascular Tone ◽  
Polymeric Nanoparticles ◽  
No Production ◽  
Cell Replication ◽  
Neuronal Communication ◽  
Physiological Processes ◽  
Promising Strategy ◽  
New Strategy ◽  
Metal Organic

Nitric oxide (NO) is involved in several physiological processes, such as the control of vascular tone, the inhibition of platelet aggregation, smooth muscle cell replication, immune response and neuronal communication. Several pathologies have been associated to dysfunctions in the endogenous NO production. Thus, there is a great interest in the development of NO-releasing drugs and in matrices which are able to stabilize and release NO locally in different tissues. In this scenario, the preparation of NO-releasing nanomaterials, such as dendrimers, liposomes, metallic, silica, and polymeric nanoparticles, zeolites and metal organic frameworks, is a promising strategy for delivering NO in diverse applications, as discussed in this work.

scholarly journals Crystallization of the human tetraspanin protein CD9

2019 ◽  
Vol 75 (4) ◽  
pp. 254-259 ◽  
Author(s):  
Rie Umeda ◽  
Tomohiro Nishizawa ◽  
Osamu Nureki
Keyword(s):  
Variable Region ◽  
Extracellular Loop ◽  
Functional Studies ◽  
Physiological Processes ◽  
Wide Range ◽  
Membrane Spanning ◽  
Cell Migration And Proliferation ◽  
First Time ◽  
Representative Member ◽  
Tetraspanin Family

The tetraspanin family of proteins with four membrane-spanning proteins function in a wide range of physiological processes in higher organisms, including cell migration and proliferation, cell fusion, fertilization and virus infection. Although the recently reported structure of CD81 unveiled the basic architecture of this family for the first time, further structural and functional studies are required in order to understand the mechanistic details of the complicated functions of the tetraspanin-family proteins. In this study, attempts were made to crystallize human CD9, a representative member of the tetraspanin family, and it was demonstrated that the truncation of a variable region in the second long extracellular loop significantly improved crystal growth.

scholarly journals Pterin-based pigmentation in animals

2021 ◽  
Vol 17 (8) ◽  
pp. 20210221
Author(s):  
Pedro Andrade ◽  
Miguel Carneiro
Keyword(s):  
Molecular Mechanisms ◽  
Potential Model ◽  
Honest Signalling ◽  
Functional Studies ◽  
Physiological Processes ◽  
History Of Research ◽  
Different Types ◽  
Genomic Studies ◽  
History Of ◽  
Advance Research

Pterins are one of the major sources of bright coloration in animals. They are produced endogenously, participate in vital physiological processes and serve a variety of signalling functions. Despite their ubiquity in nature, pterin-based pigmentation has received little attention when compared to other major pigment classes. Here, we summarize major aspects relating to pterin pigmentation in animals, from its long history of research to recent genomic studies on the molecular mechanisms underlying its evolution. We argue that pterins have intermediate characteristics (endogenously produced, typically bright) between two well-studied pigment types, melanins (endogenously produced, typically cryptic) and carotenoids (dietary uptake, typically bright), providing unique opportunities to address general questions about the biology of coloration, from the mechanisms that determine how different types of pigmentation evolve to discussions on honest signalling hypotheses. Crucial gaps persist in our knowledge on the molecular basis underlying the production and deposition of pterins. We thus highlight the need for functional studies on systems amenable for laboratory manipulation, but also on systems that exhibit natural variation in pterin pigmentation. The wealth of potential model species, coupled with recent technological and analytical advances, make this a promising time to advance research on pterin-based pigmentation in animals.

scholarly journals Circadian Clocks and the Interaction between Stress Axis and Adipose Function

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Isa Kolbe ◽  
Rebecca Dumbell ◽  
Henrik Oster
Keyword(s):  
Stress Responses ◽  
Metabolic Disorders ◽  
Stress Hormones ◽  
Circadian Clocks ◽  
Stress Disorders ◽  
Stress Axis ◽  
Physiological Conditions ◽  
Physiological Processes ◽  
Key Players ◽  
Adipose Cells

Many physiological processes and most endocrine functions show fluctuations over the course of the day. These so-called circadian rhythms are governed by an endogenous network of cellular clocks and serve as an adaptation to daily and, thus, predictable changes in the organism’s environment. Circadian clocks have been described in several tissues of the stress axis and in adipose cells where they regulate the rhythmic and stimulated release of stress hormones, such as glucocorticoids, and various adipokine factors. Recent work suggests that both adipose and stress axis clock systems reciprocally influence each other and adrenal-adipose rhythms may be key players in the development and therapy of metabolic disorders. In this review, we summarize our current understanding of adrenal and adipose tissue rhythms and clocks and how they might interact to regulate energy homoeostasis and stress responses under physiological conditions. Potential chronotherapeutic strategies for the treatment of metabolic and stress disorders are discussed.

Extracellular domains play different roles in gap junction formation and docking compatibility

2014 ◽  
Vol 458 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Donglin Bai ◽  
Ao Hong Wang
Keyword(s):  
Gap Junction ◽  
Molecular Mechanisms ◽  
Bond Forming ◽  
Functional Studies ◽  
Extracellular Domains ◽  
Physiological Processes ◽  
Recent Developments ◽  
Non Covalent Interactions ◽  
Alignment Analysis ◽  
Heterotypic Channels

GJ (gap junction) channels mediate direct intercellular communication and play an important role in many physiological processes. Six connexins oligomerize to form a hemichannel and two hemichannels dock together end-to-end to form a GJ channel. Connexin extracellular domains (E1 and E2) have been shown to be important for the docking, but the molecular mechanisms behind the docking and formation of GJ channels are not clear. Recent developments in atomic GJ structure and functional studies on a series of connexin mutants revealed that E1 and E2 are likely to play different roles in the docking. Non-covalent interactions at the docking interface, including hydrogen bonds, are predicted to form between interdocked extracellular domains. Protein sequence alignment analysis on the docking compatible/incompatible connexins indicate that the E1 domain is important for the formation of the GJ channel and the E2 domain is important in the docking compatibility in heterotypic channels. Interestingly, the hydrogen-bond forming or equivalent residues in both E1 and E2 domains are mutational hot spots for connexin-linked human diseases. Understanding the molecular mechanisms of GJ docking can assist us to develop novel strategies in rescuing the disease-linked connexin mutants.

scholarly journals Lysophosphatidic acid produced by Autotaxin acts as an allosteric modulator of its catalytic efficiency

2018 ◽  
Author(s):  
Fernando Salgado-Polo ◽  
Alex Fish ◽  
Minos-Timotheos Matsoukas ◽  
Tatjana Heidebrecht ◽  
Willem-Jan Keune ◽  
...  
Keyword(s):  
Lysophosphatidic Acid ◽  
Allosteric Regulation ◽  
Catalytic Efficiency ◽  
Feedback Mechanism ◽  
Allosteric Site ◽  
Functional Studies ◽  
Physiological Processes ◽  
Positive Feedback Mechanism ◽  
Experimental Kinetics ◽  
Kinetics Of

AbstractAutotaxin is a secreted phosphodiesterase that converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). LPA controls key cellular responses such as migration, proliferation and survival, implicating ATX-LPA signalling in various (patho)physiological processes and establishing it as a drug target. ATX structural and functional studies have revealed an orthosteric and an allosteric site, the “pocket” and the “tunnel”. Here, we revisit the kinetics of the ATX catalytic cycle in light of allosteric regulation, dissecting the different steps and pathways that lead to LPC hydrolysis. Consolidating all experimental kinetics data to a comprehensive catalytic model supported by molecular modelling simulations, suggests a positive feedback mechanism, regulated by the abundance of the LPA products activating hydrolysis of different LPC species. Our results complement and extend current understanding of ATX hydrolysis in light of the allosteric regulation by produced LPA species, and have implications for the design and application of orthosteric and allosteric ATX inhibitors.

scholarly journals Writers and Readers of DNA Methylation/Hydroxymethylation in Physiological Aging and Its Impact on Cognitive Function

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Rodrigo F. Torres ◽  
Ricardo Kouro ◽  
Bredford Kerr
Keyword(s):  
Cell Biology ◽  
Gene Expression Regulation ◽  
Critical Role ◽  
Neuronal Dysfunction ◽  
Epigenetic Landscape ◽  
Physiological Aging ◽  
Physiological Conditions ◽  
Physiological Processes ◽  
Modified Dna ◽  
Dna Modifications

The chromatin landscape has acquired deep attention from several fields ranging from cell biology to neurological and psychiatric diseases. The role that DNA modifications have on gene expression regulation has become apparent in several physiological processes, and numerous efforts have been performed to establish a relationship between DNA modifications and physiological conditions, such as cognitive performance and aging. DNA modifications are incorporated by specific sets of enzymes—the writers—and the modified DNA-interacting partners—the readers—are ultimately responsible for maintaining a functional epigenetic landscape. Therefore, understanding how these epigenetic mediators—writers and readers—are modulated in physiological aging will contribute to unraveling how aging-associated neuronal disturbances arise and contribute to the cognitive decline associated with this period of life. In this review, we focused on DNA modifications, writers and readers, highlighting that despite some methodological disparities, the evidence suggests a critical role for epigenetic mediators in the aging-associated neuronal dysfunction.

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