scholarly journals Important Role of Autophagy in Regulation of Metabolic Processes in Health, Disease and Aging

2014 ◽  
pp. 409-420 ◽  
Author(s):  
Z. PAPÁČKOVÁ ◽  
M. CAHOVÁ
Keyword(s):  
Metabolic Disorders ◽  
Storage Disease ◽  
External Environment ◽  
Nutrient Deprivation ◽  
Lysosomal Storage ◽  
Physiological Processes ◽  
Wide Range ◽  
Normal Human ◽  
Cellular Components

Autophagy is the basic catabolic mechanism that involves degradation of dysfunctional cellular components through the action of lysosome as well as supplying energy and compounds for the synthesis of essential biomacromolecules. This process enables cells to survive stress from the external environment like nutrient deprivation. Autophagy is important in the breakdown of proteins, carbohydrates and lipids as well. Furthermore, recent studies have shown that autophagy is critical in wide range of normal human physiological processes, and defective autophagy is associated with diverse diseases, including lysosomal storage disease, myopathies, neurodegeneration and various metabolic disorders. This review summarizes the most up-to-date findings on what role autophagy plays in metabolism.

scholarly journals Role of Insulin in Health and Disease: An Update

2021 ◽  
Vol 22 (12) ◽  
pp. 6403
Author(s):  
Md Saidur Rahman ◽  
Khandkar Shaharina Hossain ◽  
Sharnali Das ◽  
Sushmita Kundu ◽  
Elikanah Olusayo Adegoke ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Basic Research ◽  
Future Research ◽  
Protective Effects ◽  
Glucose Levels ◽  
Physiological Processes ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

scholarly journals The Role of Selective Protein Degradation in the Regulation of Iron and Sulfur Homeostasis in Plants

2020 ◽  
Vol 21 (8) ◽  
pp. 2771 ◽  
Author(s):  
Anna Wawrzyńska ◽  
Agnieszka Sirko
Keyword(s):  
Protein Degradation ◽  
Plant Development ◽  
Sulfur Metabolism ◽  
High Energy ◽  
26S Proteasome ◽  
Control Mechanisms ◽  
Wide Range ◽  
Ubiquitin Conjugation ◽  
Cellular Components

Plants are able to synthesize all essential metabolites from minerals, water, and light to complete their life cycle. This plasticity comes at a high energy cost, and therefore, plants need to tightly allocate resources in order to control their economy. Being sessile, plants can only adapt to fluctuating environmental conditions, relying on quality control mechanisms. The remodeling of cellular components plays a crucial role, not only in response to stress, but also in normal plant development. Dynamic protein turnover is ensured through regulated protein synthesis and degradation processes. To effectively target a wide range of proteins for degradation, plants utilize two mechanistically-distinct, but largely complementary systems: the 26S proteasome and the autophagy. As both proteasomal- and autophagy-mediated protein degradation use ubiquitin as an essential signal of substrate recognition, they share ubiquitin conjugation machinery and downstream ubiquitin recognition modules. Recent progress has been made in understanding the cellular homeostasis of iron and sulfur metabolisms individually, and growing evidence indicates that complex crosstalk exists between iron and sulfur networks. In this review, we highlight the latest publications elucidating the role of selective protein degradation in the control of iron and sulfur metabolism during plant development, as well as environmental stresses.

scholarly journals Development of Organelle Replacement Therapy Using a Stearyl-Polyhistidine Peptide against Lysosomal Storage Disease Cells

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2995 ◽  
Author(s):  
Hayashi ◽  
Okamoto ◽  
Kawano ◽  
Iwasaki
Keyword(s):  
Replacement Therapy ◽  
Lysosomal Storage Disease ◽  
Lysosomal Enzymes ◽  
Drug Delivery Systems ◽  
Metabolic Disorders ◽  
Storage Disease ◽  
Cell Penetrating Peptide ◽  
Lysosomal Storage ◽  
Hydrophobic Region ◽  
Normal Cells

We previously reported on a polyhistidine peptide, His16 peptide, as a new cell-penetrating peptide. This peptide is anticipated to be a new carrier for drug delivery systems (DDSs) for targeting intracellular lysosomes because it can transport macromolecules (e.g., liposomes) into these organelles. In the present study, we examined the application of His16 peptide as a DDS carrier against lysosomal storage disease (LSD) cells. LSDs are metabolic disorders caused by loss of specific lysosomal enzymes. For the treatment of LSD cells, we devised a system designated organelle replacement therapy (ORT). ORT is a strategy for transporting exogenous lysosomes containing all kinds of lysosomal enzymes from normal cells into endogenous lysosomes in LSD cells using His16 peptide. To develop the ORT system, we prepared His16 peptide-modified healthy lysosomes (His16-Lyso) by insertion of a stearyl-His16 peptide into a hydrophobic region in the lysosomal membrane. His16-Lyso showed cellular uptake and localization to endogenous lysosomes in LSD cells. His16-Lyso also restored the proliferation of LSD cells, which otherwise showed slower proliferation than normal cells. These results suggested that His16-Lyso replenished deficient lysosomal enzymes in LSD cells. The results further suggest that His16-Lyso are promising candidates as a treatment tool for LSD cells and to establish a foundation for ORT.

scholarly journals WC-1 and the Proximal GATA Sequence Mediate a Cis-/Trans-Acting Repressive Regulation of Light-Dependent Gene Transcription in the Dark

2019 ◽  
Vol 20 (12) ◽  
pp. 2854 ◽  
Author(s):  
Andrea Brenna ◽  
Claudio Talora
Keyword(s):  
Transcriptional Activation ◽  
Dark Light ◽  
Consensus Sequences ◽  
Physiological Processes ◽  
Photo Sensor ◽  
Wide Range ◽  
White Collar Complex ◽  
Light Stimuli ◽  
Nucleotide Repeats

Light influences a wide range of physiological processes from prokaryotes to mammals. Neurospora crassa represents an important model system used for studying this signal pathway. At molecular levels, the WHITE COLLAR Complex (WCC), a heterodimer formed by WC-1 (the blue light photo-sensor) and WC-2 (the transcriptional activator), is the critical positive regulator of light-dependent gene expression. GATN (N indicates any other nucleotide) repeats are consensus sequences within the promoters of light-dependent genes recognized by the WCC. The distal GATN is also known as C-box since it is involved in the circadian clock. However, we know very little about the role of the proximal GATN, and the molecular mechanism that controls the transcription of light-induced genes during the dark/light transition it is still unclear. Here we showed a first indication that mutagenesis of the proximal GATA sequence within the target promoter of the albino-3 gene or deletion of the WC-1 zinc finger domain led to a rise in expression of light-dependent genes already in the dark, effectively decoupling light stimuli and transcriptional activation. This is the first observation of cis-/trans-acting repressive machinery, which is not consistent with the light-dependent regulatory mechanism observed in the eukaryotic world so far.

scholarly journals Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2749 ◽  
Author(s):  
Miguel A. Ortega ◽  
Oscar Fraile-Martínez ◽  
Irene Naya ◽  
Natalio García-Honduvilla ◽  
Melchor Álvarez-Mon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Health Concern ◽  
Public Health Concern ◽  
Wide Range

Obesity is a condition of rising prevalence worldwide, with important socioeconomic implications, being considered as a growing public health concern. Frequently, obesity brings other complications in addition to itself—like Type 2 Diabetes Mellitus (T2DM)—sharing origin, risk factors and pathophysiological mechanisms. In this context, some authors have decided to include both conditions as a unique entity known as “diabesity”. In fact, understanding diabesity as a single disease is possible to maximise the benefits from therapies received in these patients. Gut microbiota plays a key role in individual’s health, and their alterations, either in its composition or derived products are related to a wide range of metabolic disorders like T2DM and obesity. The present work aims to collect the different changes reported in gut microbiota in patients with T2DM associated with obesity and their possible role in the onset, development, and establishment of the disease. Moreover, current research lines to modulate gut microbiota and the potential clinical translation derived from the knowledge of this system will also be reviewed, which may provide support for a better clinical management of such a complex condition.

scholarly journals Lysosome function in glomerular health and disease

2021 ◽  
Author(s):  
Catherine Meyer-Schwesinger
Keyword(s):  
Current Knowledge ◽  
Lysosomal Storage Diseases ◽  
Cell Types ◽  
Lysosomal Storage ◽  
Membrane Repair ◽  
Glomerular Cell ◽  
Wide Range ◽  
Center Position ◽  
Health And Disease

AbstractThe lysosome represents an important regulatory platform within numerous vesicle trafficking pathways including the endocytic, phagocytic, and autophagic pathways. Its ability to fuse with endosomes, phagosomes, and autophagosomes enables the lysosome to break down a wide range of both endogenous and exogenous cargo, including macromolecules, certain pathogens, and old or damaged organelles. Due to its center position in an intricate network of trafficking events, the lysosome has emerged as a central signaling node for sensing and orchestrating the cells metabolism and immune response, for inter-organelle and inter-cellular signaling and in membrane repair. This review highlights the current knowledge of general lysosome function and discusses these findings in their implication for renal glomerular cell types in health and disease including the involvement of glomerular cells in lysosomal storage diseases and the role of lysosomes in nongenetic glomerular injuries.

A comprehensive overview of PPM1A: From structure to disease

2021 ◽  
pp. 153537022110618
Author(s):  
Mao Li ◽  
Xingfeng Xu ◽  
Yan Su ◽  
Xiaoyun Shao ◽  
Yali Zhou ◽  
...  
Keyword(s):  
Negative Regulator ◽  
Comprehensive Overview ◽  
Physiological Processes ◽  
Stress Response Pathway ◽  
Family Protein ◽  
Wide Range ◽  
Proliferation And Apoptosis ◽  
Insight Into ◽  
Phosphate Groups

PPM1A (magnesium-dependent phosphatase 1 A, also known as PP2Cα) is a member of the Ser/Thr protein phosphatase family. Protein phosphatases catalyze the removal of phosphate groups from proteins via hydrolysis, thus opposing the role of protein kinases. The PP2C family is generally considered a negative regulator in the eukaryotic stress response pathway. PPM1A can bind and dephosphorylate various proteins and is therefore involved in the regulation of a wide range of physiological processes. It plays a crucial role in transcriptional regulation, cell proliferation, and apoptosis and has been suggested to be closely related to the occurrence and development of cancers of the lung, bladder, and breast, amongst others. Moreover, it is closely related to certain autoimmune diseases and neurodegenerative diseases. In this review, we provide an insight into currently available knowledge of PPM1A, including its structure, biological function, involvement in signaling pathways, and association with diseases. Lastly, we discuss whether PPM1A could be targeted for therapy of certain human conditions.

Glucocerebrosidase, a new player changing the old rules in Lewy body diseases

2013 ◽  
Vol 394 (7) ◽  
pp. 807-818 ◽  
Author(s):  
Na-Young Yang ◽  
Yu-Na Lee ◽  
He-Jin Lee ◽  
Yoon Suk Kim ◽  
Seung-Jae Lee
Keyword(s):  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Storage Disease ◽  
Lewy Bodies ◽  
Mechanisms Of Action ◽  
Lysosomal Storage ◽  
Gene Encoding ◽  
Glycolipid Metabolism ◽  
Lewy Body Diseases

AbstractMutations in the gene encoding glucocerebrosidase (GBA1) cause Gaucher disease (GD), a lysosomal storage disease with recessive inheritance. Glucocerebrosidase (GCase) is a lysosomal lipid hydrolase that digests glycolipid substrates, such as glucosylceramide and glucosylsphingosine.GBA1mutations have been implicated in Lewy body diseases (LBDs), such as Parkinson’s disease and dementia with Lewy bodies. Parkinsonism occurs more frequently in certain types of GD, andGBA1mutation carriers are more likely to have LBDs than non-carriers. Furthermore, GCase is often found in Lewy bodies, which are composed of α-synuclein fibrils as well as a variety of proteins and vesicles. In this review, we discuss potential mechanisms of action ofGBA1mutations in LBDs with particular emphasis on α-synuclein aggregation by reviewing the current literature on the role of GCase in lysosomal functions and glycolipid metabolism.

scholarly journals Role of Vacha (Acorus calamus Linn.) in Neurological and Metabolic Disorders: Evidence from Ethnopharmacology, Phytochemistry, Pharmacology and Clinical Study

2020 ◽  
Vol 9 (4) ◽  
pp. 1176 ◽  
Author(s):  
Vineet Sharma ◽  
Rohit Sharma ◽  
DevNath Singh Gautam ◽  
Kamil Kuca ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Metabolic Disorders ◽  
Literature Survey ◽  
Acorus Calamus ◽  
Extensive Literature ◽  
Compelling Evidence ◽  
Liver Disorders ◽  
Active Constituents ◽  
Wide Range

Vacha (Acorus calamus Linn. (Acoraceae)) is a traditional Indian medicinal herb, which is practiced to treat a wide range of health ailments, including neurological, gastrointestinal, respiratory, metabolic, kidney, and liver disorders. The purpose of this paper is to provide a comprehensive up-to-date report on its ethnomedicinal use, phytochemistry, and pharmacotherapeutic potential, while identifying potential areas for further research. To date, 145 constituents have been isolated from this herb and identified, including phenylpropanoids, sesquiterpenoids, and monoterpenes. Compelling evidence is suggestive of the biopotential of its various extracts and active constituents in several metabolic and neurological disorders, such as anticonvulsant, antidepressant, antihypertensive, anti-inflammatory, immunomodulatory, neuroprotective, cardioprotective, and anti-obesity effects. The present extensive literature survey is expected to provide insights into the involvement of several signaling pathways and oxidative mechanisms that can mitigate oxidative stress, and other indirect mechanisms modulated by active biomolecules of A. calamus to improve neurological and metabolic disorders.

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