Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2488 - 2488

Published: Sept. 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.

Language: Английский

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Mitochondrial quality control in human health and disease

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: May 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.

Language: Английский

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Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 511 - 511

Published: March 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

Language: Английский

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Protein translation: biological processes and therapeutic strategies for human diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 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.

Language: Английский

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Parkinson's Disease Modeling Using Directly Converted 3D Induced Dopaminergic Neuron Organoids and Assembloids

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

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Mitochondria‐Related Genome‐Wide Mendelian Randomization Identifies Putatively Causal Genes for Neurodegenerative Diseases

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

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

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10809 - 10809

Published: June 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.

Language: Английский

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Targeting the Labile Iron Pool with Engineered DFO Nanosheets to Inhibit Ferroptosis for Parkinson's Disease Therapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(41)

Published: Sept. 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.

Language: Английский

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

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1071 - 1071

Published: Jan. 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

Language: Английский

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Genetically modified non-human primate models for research on neurodegenerative diseases

动物学研究, Journal Year: 2024, Volume and Issue: 45(2), P. 263 - 274

Published: Jan. 1, 2024

Neurodegenerative diseases (NDs) are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), amyotrophic lateral sclerosis (ALS). Currently, there no therapies available can delay, stop, or reverse the pathological progression NDs in clinical settings. As population ages, imposing huge burden on public health systems affected families. Animal models important tools for preclinical investigations to understand pathogenesis test potential treatments. While numerous rodent have been developed enhance our understanding mechanisms, limited success translating findings from animal practice suggests is still need bridge this translation gap. Old World non-human primates (NHPs), such as rhesus, cynomolgus, vervet monkeys, phylogenetically, physiologically, biochemically, behaviorally most relevant humans. This particularly evident similarity structure function their central nervous systems, rendering species uniquely valuable neuroscience research. Recently, development several genetically modified NHP has successfully recapitulated key pathologies revealed novel mechanisms. review focuses efficacy NHPs modeling insights gained, well challenges associated with generation complexities involved subsequent analysis.

Language: Английский

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