Soot nanoparticles promote ferroptosis in dopaminergic neurons via alteration of m6A RNA methylation in Parkinson’s disease DOI

Jiezhu Feng,

Piao Zhang,

Kunlin Chen

и другие.

Journal of Hazardous Materials, Год журнала: 2024, Номер 473, С. 134691 - 134691

Опубликована: Май 22, 2024

Язык: Английский

Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities DOI Creative Commons
Vicente Javier Clemente‐Suárez, Laura Redondo-Flórez, Ana Isabel Beltrán-Velasco

и другие.

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

Mitochondrial quality control in human health and disease DOI Creative Commons
Bohao Liu,

Chen-Zhen Xu,

Yi Liu

и другие.

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

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders DOI Creative Commons
Jessica R. Cohen,

Annette Mathew,

Kirk D. Dourvetakis

и другие.

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

Protein translation: biological processes and therapeutic strategies for human diseases DOI Creative Commons

Xuechao Jia,

Xinyu He,

Chuntian Huang

и другие.

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

Mitochondria‐Related Genome‐Wide Mendelian Randomization Identifies Putatively Causal Genes for Neurodegenerative Diseases DOI Open Access
Zheyi Wang, Yize Sun,

Zetai Bai

и другие.

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

Parkinson's Disease Modeling Using Directly Converted 3D Induced Dopaminergic Neuron Organoids and Assembloids DOI Creative Commons
Hongwon Kim,

Soi Kang,

Byounggook Cho

и другие.

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

Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer’s, Parkinson’s, and Huntington’s Diseases and Amyotrophic Lateral Sclerosis DOI Open Access

Alexandru Vlad Ciurea,

Aurel George Mohan, Razvan-Adrian Covache-Busuioc

и другие.

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

Sphingolipids in neurodegenerative diseases DOI Creative Commons
Xueyang Pan, Debdeep Dutta, Shenzhao Lu

и другие.

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

Targeting the Labile Iron Pool with Engineered DFO Nanosheets to Inhibit Ferroptosis for Parkinson's Disease Therapy DOI
Lei Li, Jiali Yuan, Zhijun Dai

и другие.

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

The Potentiality of Natural Products and Herbal Medicine as Novel Medications for Parkinson’s Disease: A Promising Therapeutic Approach DOI Open Access

Y. So,

Jae-Ung Lee,

Ga-Seung Yang

и другие.

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