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Biomolecules Nov 2023Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular... (Review)
Review
Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular control. There are over 1000 known proteins that either reside within the mitochondria or are transiently associated with it. These mitochondrial proteins represent a functional subcellular protein network (mtProteome) that is encoded by mitochondrial and nuclear genomes and significantly varies between cell types and conditions. In neurons, the high metabolic demand and differential energy requirements at the synapses are met by specific modifications to the mtProteome, resulting in alterations in the expression and functional properties of the proteins involved in energy production and quality control, including fission and fusion. The composition of mtProteomes also impacts the localization of mitochondria in axons and dendrites with a growing number of neurodegenerative diseases associated with changes in mitochondrial proteins. This review summarizes the findings on the composition and properties of mtProteomes important for mitochondrial energy production, calcium and lipid signaling, and quality control in neural cells. We highlight strategies in mass spectrometry (MS) proteomic analysis of mtProteomes from cultured cells and tissue. The research into mtProteome composition and function provides opportunities in biomarker discovery and drug development for the treatment of metabolic and neurodegenerative disease.
Topics: Humans; Proteome; Neurodegenerative Diseases; Proteomics; Mitochondria; Neurons; Mitochondrial Proteins
PubMed: 38002320
DOI: 10.3390/biom13111638 -
Biomedicine & Pharmacotherapy =... Sep 2023Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs... (Review)
Review
Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding the pathological mechanisms of NDDs in recent years, the development of targeted and effective drugs for their treatment remains challenging. Kaempferol is a flavonoid whose derivatives include kaempferol-O-rhamnoside, 3-O-β-rutinoside/6-hydroxykaempferol 3,6-di-O-β-d-glucoside, and kaempferide. Emerging studies have suggested that kaempferol and its derivatives possess neuroprotective properties and may have potential therapeutic benefits in NDDs. Here, we aimed to provide a theoretical basis for the use of kaempferol and its derivatives in the clinical treatment of NDDs. We systematically reviewed the literature in the PubMed, Web of Science, and Science Direct databases until June 2022 using the search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," and "biosynthesis" according to the reporting items for systematic review (PRISMA) standard. Based on combined results of in vivo and in vitro studies, we summarize the basic mechanisms and targets of kaempferol and its derivatives in the management of AD, PD, HD, and ALS. Kaempferol and its derivatives exert a neuroprotective role mainly by preventing the deposition of amyloid fibrils (such as Aβ, tau, and α-synuclein), inhibiting microglia activation, reducing the release of inflammatory factors, restoring the mitochondrial membrane to prevent oxidative stress, protecting the blood-brain barrier, and inhibiting specific enzyme activities (such as cholinesterase). Kaempferol and its derivatives are promising natural neuroprotective agents. By determining their pharmacological mechanism, kaempferol and its derivatives may be new candidate drugs for the treatment of NDDs.
Topics: Humans; Neurodegenerative Diseases; Neuroprotective Agents; Amyotrophic Lateral Sclerosis; Kaempferols; Alzheimer Disease; Parkinson Disease; Huntington Disease
PubMed: 37494786
DOI: 10.1016/j.biopha.2023.115215 -
International Journal of Molecular... Dec 2023Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and... (Review)
Review
Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relationship exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms". Bibliographic references to relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.
Topics: Humans; Atrial Fibrillation; Cardiac Conduction System Disease; Heart Diseases; Mitochondrial Diseases; Oxidative Stress
PubMed: 38203704
DOI: 10.3390/ijms25010535 -
Frontiers in Veterinary Science 2024Cryopreservation of sperm is an essential technique in assisted reproduction in cattle. The objective of the study was to systematically review and synthesize the...
Cryopreservation of sperm is an essential technique in assisted reproduction in cattle. The objective of the study was to systematically review and synthesize the literature on bull semen quality evaluation based on the comparison of morphological and metabolic parameters of cryopreserved bovine spermatozoa such as DNA integrity, mitochondrial status, plasma membrane alterations, total motility, and morphology (% of abnormal cells). The electronic databases PubMed, Web of Sciences, Scopus, and Google Scholar were searched up to December 2023. Studies and references were included if they reported the following parameters: DNA integrity, mitochondrial status, plasma membrane alterations, total motility, and morphological aberrations (% of abnormal cells) for conventional cryopreserved bovine spermatozoa. After an electronic search, out of 1,526 original studies, only 40 were included in the meta-analysis. Standardized mean differences (SMD) with 95% confidence intervals were estimated for the chosen studies, and a meta-analysis was performed using a random effects model. The tau-squared (tau) and inconsistency index () quantified heterogeneity among different studies. The regression analysis for the evaluated parameters showed a positive correlation between mitochondrial membrane potential (MMP), total motility, and abnormal morphology and a negative correlation between DNA fragmentation index (DFI) and total motility and MMP. Moreover, subgroup analysis demonstrated similar associations for dairy and non-dairy bull breeds, albeit with lower values. The presence of publication bias was confirmed by Egger's test, except for the MMP parameter. A multi-parametric analysis of morphological and metabolic parameters can address the existing limitations of cryopreserved bovine spermatozoa quality assessment. Combining imaging flow cytometry (IFC) with standardization of sperm pre-processing and optimization of the experimental protocols may help to differentiate sperm from cellular debris and cytoplasmic droplets of similar size and alleviate limitations demonstrated by conventional sperm analysis.
PubMed: 38721151
DOI: 10.3389/fvets.2024.1371586 -
International Journal of Molecular... Sep 2023Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine... (Review)
Review
Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine causes complex multiorgan toxicity, including in the heart where the blockade of the sodium channels causes increased catecholamine levels and alteration in calcium homeostasis, thus inducing an increased oxygen demand. Moreover, there is evidence to suggest that mitochondria alterations play a crucial role in the development of cocaine cardiotoxicity. We performed a systematic review according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) scheme to evaluate the mitochondrial mechanisms determining cocaine cardiotoxicity. Among the initial 106 articles from the Pubmed database and the 17 articles identified through citation searching, 14 final relevant studies were extensively reviewed. Thirteen articles included animal models and reported the alteration of specific mitochondria-dependent mechanisms such as reduced energy production, imbalance of membrane potential, increased oxidative stress, and promotion of apoptosis. However, only one study evaluated human cocaine overdose samples and observed the role of cocaine in oxidative stress and the induction of apoptosis though mitochondria. Understanding the complex processes mediated by mitochondria through forensic analysis and experimental models is crucial for identifying potential therapeutic targets to mitigate or reverse cocaine cardiotoxicity in humans.
Topics: Animals; Humans; Cardiotoxicity; Cocaine; Cocaine-Related Disorders; Heart; Mitochondria; Oxidative Stress
PubMed: 37833964
DOI: 10.3390/ijms241914517 -
Frontiers in Pharmacology 2023Autophagy is a cellular process where damaged organelles or unwanted proteins are packaged into a double-membrane structure and transported to lysosomes for...
Autophagy is a cellular process where damaged organelles or unwanted proteins are packaged into a double-membrane structure and transported to lysosomes for degradation. Autophagy plays a regulatory role in various hematologic malignancies, including acute myeloid leukemia (AML). However, there are few bibliometric studies on the role of autophagy in AML. The purpose of this study is to clarify the role of autophagy in acute myeloid leukemia through bibliometric analysis. The literature on autophagy and AML research from 2003 to 2023 was searched in Web of Science Core Collection, and bibliometric tools such as VOSviewer 1.6.18, Cite Space (6.1.R3), RStudio (R package bibliometrix), and Scimago Graphica were used to understand the current status and hotspots of autophagy and AML research. The study conducted an analysis of various dimensions including the quantity of publications, countries, institutions, journals, authors, co-references, keywords, and to predict future development trends in this field by drawing relevant visualization maps. A total of 343 articles were obtained, published in 169 journals, written by 2,323 authors from 295 institutions in 43 countries. The journals with the most publications were Blood and Oncotarget. China had the most publications, and Chongqing Medical University and Sun Yat-sen University had the most publications. The author with the highest number of publications was Tschan, Mario P. The main types of research included clinical research, experiments, experiments, public database information, and reviews, and the forms of therapeutic effects mainly focused on genetic regulation, traditional Chinese medicine combination, autophagy inhibitors, and drug targets. The research hotspots of autophagy and AML in the past 17 years have focused on genetic regulation, autophagy inhibition, and targeted drugs. Chemotherapy resistance and mitochondrial autophagy will be the forefront of research. The gradual increase in the literature on autophagy and AML research and the decline after 2022 could be a result of authors focusing more on the type of research and the quality of the literature. The current research hotspots are mainly genetic regulation, autophagy inhibition, and autophagy-related targeted drugs. In future, autophagy will remain the focus of the AML field, with research trends likely to focus more on AML chemotherapy resistance and mitochondrial autophagy.
PubMed: 38322702
DOI: 10.3389/fphar.2023.1291195 -
Biomedicine & Pharmacotherapy =... Jul 2024Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising... (Review)
Review
Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aβ, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.
Topics: Activating Transcription Factor 4; Humans; Central Nervous System Diseases; Animals; Phytochemicals; Neuroprotective Agents
PubMed: 38795641
DOI: 10.1016/j.biopha.2024.116811 -
American Journal of Cancer Research 2024Cancer is one of the leading causes of death worldwide. In recent years, African countries have been faced with a rapid increase in morbidity and mortality due to this... (Review)
Review
Cancer is one of the leading causes of death worldwide. In recent years, African countries have been faced with a rapid increase in morbidity and mortality due to this pathology. Management is often complicated by the high treatment costs, side effects and the increasing occurrence of resistance to treatments. The identification of new active ingredients extracted from endemic medicinal plants is definitively an interesting approach for the implementation of new therapeutic strategies: their extraction is often lower cost; their identification is based on an ethnobotanical history and a tradipratic approach; their use by low-income populations is simpler; this can help in the development of new synthetic molecules that are more active, more effective and with fewer side effects. The objective of this review is to document the molecules derived from African medicinal plants whose anti-cancer activities and the mechanisms of molecular actions have been identified. From the scientific databases , PubMed and Google Scholar, we searched for publications on compounds isolated from African medicinal plants and having activity on cancer cells in culture. The data were analyzed in particular with regard to the cytotoxicity of the compounds and their mode of action. A total of 90 compounds of these African medicinal plants were selected. They come from nine chemical groups: alkaloids, flavonoids, polyphenols, quinones, saponins, steroids, terpenoids, xanthones and organic sulfides. These compounds have been associated with several cellular effects: i) Cytotoxicity, including caspase activation, alteration of mitochondrial membrane potential, and/or induction of reactive oxygen species (ROS); ii) Anti-angiogenesis; iii) Anti-metastatic properties. This review points out that the cited African plants are rich in active ingredients with anticancer properties. It also stresses that screening of these anti-tumor active ingredients should be continued at the continental scale. Altogether, this work provides a rational basis for the selection of phytochemical compounds for use in clinical trials.
PubMed: 38590420
DOI: 10.62347/AUHB5811 -
CNS Neuroscience & Therapeutics Mar 2024Mitochondrial complex III (CIII) deficiency is an autosomal recessive disease characterized by symptoms such as ataxia, cognitive dysfunction, and spastic paraplegia....
BACKGROUND
Mitochondrial complex III (CIII) deficiency is an autosomal recessive disease characterized by symptoms such as ataxia, cognitive dysfunction, and spastic paraplegia. Multiple genes are associated with complex III defects. Among them, the mutation of TTC19 is a rare subtype.
METHODS
We screened a Chinese boy with weakness of limbs and his non-consanguineous parents by whole exome sequencing and targeted sequencing.
RESULTS
We report a Chinese boy diagnosed with mitochondrial complex III defect type 2 carrying a homozygous variant (c.719-732del, p.Leu240Serfs*17) of the TTC19 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance. We provide his clinical manifestation.
CONCLUSIONS
A new type of TTC19 mutation (c.719-732del, p.Leu240Serfs*17) was found, which enriched the TTC19 gene mutation spectrum and provided new data for elucidating the pathogenesis of CIII-deficient diseases.
Topics: Male; Humans; Electron Transport Complex III; Membrane Proteins; Mutation; Peripheral Nervous System Diseases; Movement Disorders; Pedigree; Mitochondrial Diseases
PubMed: 37927170
DOI: 10.1111/cns.14425