Journal of Hazardous Materials, Год журнала: 2024, Номер 473, С. 134691 - 134691
Опубликована: Май 22, 2024
Язык: Английский
Biomedicines, Год журнала: 2023, Номер 11(9), С. 2488 - 2488
Опубликована: Сен. 7, 2023
Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated the pathogenesis various brain diseases, including neurodegenerative disorders, stroke, psychiatric illnesses. This review paper provides comprehensive overview intricate relationship between disease, focusing on underlying pathological mechanisms exploring potential therapeutic opportunities. The covers key topics such as mitochondrial DNA mutations, impaired oxidative phosphorylation, dynamics, calcium dysregulation, reactive oxygen species generation context disease. Additionally, it discusses emerging strategies targeting dysfunction, protective agents, metabolic modulators, gene therapy approaches. By critically analysing existing literature recent advancements, this aims to enhance our understanding multifaceted disease shed light novel interventions.
Язык: Английский
Процитировано
77
Military Medical Research, Год журнала: 2024, Номер 11(1)
Опубликована: Май 29, 2024
Abstract Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable vital life processes such cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key like biogenesis, dynamics, mitophagy, which have garnered increasing attention from researchers unveil specific molecular mechanisms. this review, we present comprehensive summary of primary mechanisms functions regulators involved major components MQC. Furthermore, critical regulated by MQC its diverse roles progression systemic diseases been described detail. We discuss agonists antagonists targeting MQC, aiming explore potential therapeutic research prospects enhancing stabilize function.
Язык: Английский
Процитировано
37
Cells, Год журнала: 2024, Номер 13(6), С. 511 - 511
Опубликована: Март 14, 2024
Neuroinflammatory and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s (PD), traumatic brain injury (TBI) Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions these pathogeneses is currently not clearly understood. These show dysregulated inflammatory responses, activation neurons, glial cells, neurovascular unit damage associated with excessive release proinflammatory cytokines, chemokines, neurotoxic mediators, infiltration peripheral immune cells into brain, as well entry mediators through damaged endothelial blood–brain barrier tight junction proteins. Activation leads to many molecules that cause neuroinflammation neurodegeneration. Gulf War Illness (GWI) myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) also dysfunctions. Currently, there no effective disease-modifying therapeutic options available for diseases. Human induced pluripotent stem cell (iPSC)-derived astrocytes, microglia, pericytes used models drug discovery. This review highlights certain recent trends in neuroinflammatory responses iPSC-derived applications
Язык: Английский
Процитировано
36
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Фев. 23, 2024
Abstract Protein translation is a tightly regulated cellular process that essential for gene expression and protein synthesis. The deregulation of this increasingly recognized as critical factor in the pathogenesis various human diseases. In review, we discuss how deregulated can lead to aberrant synthesis, altered functions, disease progression. We explore key mechanisms contributing translation, including functional alterations factors, tRNA, mRNA, ribosome function. Deregulated leads abnormal expression, disrupted signaling, perturbed functions- all which contribute pathogenesis. development profiling techniques along with mass spectrometry-based proteomics, mRNA sequencing single-cell approaches have opened new avenues detecting diseases related errors. Importantly, highlight recent advances therapies targeting translation-related disorders their potential applications neurodegenerative diseases, cancer, infectious cardiovascular Moreover, growing interest lies targeted aimed at restoring precise control over diseased cells discussed. conclusion, comprehensive review underscores role its therapeutic target. Advancements understanding molecular deregulation, coupled therapies, offer promising improving outcomes Additionally, it will unlock doors possibility precision medicine by offering personalized deeper underpinnings future.
Язык: Английский
Процитировано
30
Movement Disorders, Год журнала: 2025, Номер unknown
Опубликована: Янв. 22, 2025
Mitochondrial dysfunction is increasingly recognized as a key factor in neurodegenerative diseases (NDDs), underscoring the therapeutic potential of targeting mitochondria-related genes. This study aimed to identify novel biomarkers and drug targets for these through comprehensive analysis that integrated genome-wide Mendelian randomization (MR) with genes associated mitochondrial function. Using existing publicly available association studies (GWAS) summary statistics data on 1136 genes, we initially identified subset related function exhibited significant associations NDDs. We then conducted colocalization summary-data-based (SMR) analyses using expression quantitative trait loci (eQTL) validate causal role candidate Additionally, assessed druggability encoded proteins prioritize further exploration. Genetically predicted levels 10 were found be significantly risk Elevated DMPK LACTB2 increased Alzheimer's disease risk. Higher NDUFAF2, BCKDK, MALSU1, along lower TTC19, raised Parkinson's ACLY both amyotrophic lateral sclerosis multiple (MS) risks, while decreased MCL1, TOP3A, VWA8 MS These primarily impact energy metabolism. Notably, several druggable protein are being explored NDDs treatment. data-driven MR demonstrated this could serve pharmacological prevention treatment © 2025 International Parkinson Movement Disorder Society.
Язык: Английский
Процитировано
3
Advanced Science, Год журнала: 2025, Номер unknown
Опубликована: Фев. 18, 2025
Abstract Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons and accumulation α‐synuclein aggregates, yet current models inadequately mimic complex human brain environment. Recent advances in organoid offer a more physiologically relevant platform for studying PD, however, iPSC‐derived organoids require long maturation times may not accurately represent aged brain's epigenetics cellular contexts, limiting their applicability modeling late‐onset diseases like PD. In this study, novel approach generating 3D‐induced (iDA) neuron directly from fibroblasts presented. It confirmed that these 3D iDA closely resemble replicate PD pathologies. Furthermore, model extended incorporating astrocytes to create neuron‐astrocyte assembloids, recognizing critical role glial cells neurodegenerative processes. identified assembloids control with A53T mutant iDAs demonstrated neuroprotective effects healthy astrocytes. contrast, progressively contributed neuronal degeneration synucleinopathy 3D‐iDA assembloids. These findings suggest converted provide robust pathogenesis evaluating therapeutic interventions.
Язык: Английский
Процитировано
3
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 10809 - 10809
Опубликована: Июнь 28, 2023
Neurodegenerative diseases are, according to recent studies, one of the main causes disability and death worldwide. Interest in molecular genetics has started experience exponential growth thanks numerous advancements technology, shifts understanding disease as a phenomenon, change perspective regarding gene editing advantages this action. The aim paper is analyze newest approaches sciences four most important neurodegenerative disorders: Alzheimer’s disease, Parkinson’s Huntington’s amyotrophic lateral sclerosis. We intend through review focus on treatment, diagnosis, predictions large group diseases, order obtain more accurate analysis identify emerging signs that could lead better outcome increase both quality life span patient. Moreover, provide evidence future possible novel therapies target specific genes be useful taken into consideration when classical fail shed light.
Язык: Английский
Процитировано
39
Frontiers in Neuroscience, Год журнала: 2023, Номер 17
Опубликована: Фев. 16, 2023
Neurodegenerative Diseases (NDDs) are a group of disorders that cause progressive deficits neuronal function. Recent evidence argues sphingolipid metabolism is affected in surprisingly broad set NDDs. These include some lysosomal storage diseases (LSDs), hereditary sensory and autonomous neuropathy (HSAN), spastic paraplegia (HSP), infantile neuroaxonal dystrophy (INAD), Friedreich’s ataxia (FRDA), as well forms amyotrophic lateral sclerosis (ALS) Parkinson’s disease (PD). Many these have been modeled Drosophila melanogaster associated with elevated levels ceramides. Similar changes also reported vertebrate cells mouse models. Here, we summarize studies using fly models and/or patient samples which demonstrate the nature defects metabolism, organelles implicated, cell types initially affected, potential therapeutics for diseases.
Язык: Английский
Процитировано
24
Advanced Materials, Год журнала: 2024, Номер 36(41)
Опубликована: Сен. 2, 2024
Ferroptosis in neurons is considered one of the key factors that induces Parkinson's disease (PD), which caused by excessive iron accumulation intracellular labile pool (LIP). The ions released from LIP lead to aberrant generation reactive oxygen species (ROS) trigger ferroptosis and exacerbate PD progression. Herein, a pioneering design multifunctional nanoregulator deferoxamine (DFO)-integrated nanosheets (BDPR NSs) presented target restrict protect against PD. BDPR NSs are constructed incorporating brain-targeting peptide DFO into polydopamine-modified black phosphorus nanosheets. These can sequester free ions, thereby ameliorating overload regulating metabolism. Furthermore, decrease lipid peroxidation mitigating ROS accumulation. More importantly, specifically accumulate mitochondria suppress mitochondrial In vivo experiments demonstrated highly efficiently mitigated dopaminergic neuronloss its associated behavioral disorders modulating inhibiting ferroptosis. Thus, BDPR-based nanovectors holds promise as potential avenue for advancing therapy.
Язык: Английский
Процитировано
14
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 1071 - 1071
Опубликована: Янв. 15, 2024
As the global population ages, prevalence of Parkinson’s disease (PD) is steadily on rise. PD demonstrates chronic and progressive characteristics, many cases can transition into dementia. This increases societal economic burdens, emphasizing need to find effective treatments. Among widely recognized causes abnormal accumulation proteins, autophagy dysfunction accelerates this accumulation. The resultant Lewy bodies are also commonly found in Alzheimer’s patients, suggesting an increased potential for onset Additionally, production free radicals due mitochondrial contributes neuronal damage degeneration. activation astrocytes M1 phenotype microglia promote dopamine neurons. drugs currently used only delay clinical progression exacerbation without targeting its root cause, come with various side effects. Thus, there a demand treatments fewer effects, much offered by natural products. In study, we reviewed total 14 articles related herbal medicines products investigated their relevance possible treatment. results showed that against lysosomal disorder, dysfunction, inflammation, key mechanisms underlying PD. Therefore, reduce neurotoxicity might improve both motor non-motor symptoms associated Furthermore, these products, multi-target enhance bioavailability, inhibit antibiotic resistance, additionally eliminate making them good alternative therapies
Язык: Английский
Процитировано
12