The mitophagy pathway and its implications in human diseases

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Авг. 16, 2023

Abstract Mitochondria are dynamic organelles with multiple functions. They participate in necrotic cell death and programmed apoptotic, crucial for metabolism survival. Mitophagy serves as a cytoprotective mechanism to remove superfluous or dysfunctional mitochondria maintain mitochondrial fine-tuning numbers balance intracellular homeostasis. Growing evidences show that mitophagy, an acute tissue stress response, plays important role maintaining the health of network. Since timely removal abnormal is essential survival, cells have evolved variety mitophagy pathways ensure can be activated time under various environments. A better understanding diseases treatment therapeutic target design. In this review, we summarize molecular mechanisms mitophagy-mediated elimination, how maintains homeostasis at system levels organ, what alterations related development diseases, including neurological, cardiovascular, pulmonary, hepatic, renal disease, etc., recent advances. Finally, potential clinical applications outline conditions regulators enter trials. Research advances signaling transduction will developing new strategies precision medicine.

Язык: Английский

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Mitochondrial dysfunction and neurological disorders: A narrative review and treatment overview

Life Sciences, Год журнала: 2023, Номер 334, С. 122257 - 122257

Опубликована: Ноя. 8, 2023

Язык: Английский

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Iron homeostasis imbalance and ferroptosis in brain diseases

MedComm, Год журнала: 2023, Номер 4(4)

Опубликована: Июнь 26, 2023

Brain iron homeostasis is maintained through the normal function of blood-brain barrier and regulation at systemic cellular levels, which fundamental to brain function. Excess can catalyze generation free radicals Fenton reactions due its dual redox state, thus causing oxidative stress. Numerous evidence has indicated diseases, especially stroke neurodegenerative are closely related mechanism imbalance in brain. For one thing, diseases promote accumulation. another, accumulation amplifies damage nervous system exacerbates patients' outcomes. In addition, triggers ferroptosis, a newly discovered iron-dependent type programmed cell death, neurodegeneration received wide attention recent years. this context, we outline metabolism focus on current stroke, Alzheimer's disease, Parkinson's disease. Meanwhile, also discuss ferroptosis simultaneously enumerate drugs for chelators inhibitors.

Язык: Английский

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Targeting Mitochondrial Dysfunction and Reactive Oxygen Species for Neurodegenerative Disease Treatment

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7952 - 7952

Опубликована: Июль 21, 2024

Alzheimer's disease (AD) and Parkinson's (PD) are the most common neurodegenerative diseases, they affect millions of people worldwide, particularly older individuals. Therefore, there is a clear need to develop novel drug targets for treatment age-related diseases. Emerging evidence suggests that mitochondrial dysfunction reactive oxygen species (ROS) generation play central roles in onset progression Mitochondria key regulators respiratory function, cellular energy adenosine triphosphate production, maintenance redox homeostasis, which essential cell survival. Mitochondrial morphology function tightly regulated by maintaining balance among fission, fusion, biogenesis, mitophagy. In this review, we provide an overview main functions mitochondria, with focus on recent progress highlighting critical role ROS-induced oxidative stress, dysregulated dynamics, apoptosis, mitochondria-associated inflammation, impaired pathogenesis such as AD PD. We also discuss potential fusion biogenesis enhancers, fission inhibitors, mitochondria-targeted antioxidants drugs these

Язык: Английский

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The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson’s Disease Pathogenesis

Nutrients, Год журнала: 2023, Номер 15(16), С. 3585 - 3585

Опубликована: Авг. 15, 2023

Parkinson’s disease (PD) is a degenerative condition resulting from the loss of dopaminergic neurons. This neuronal leads to motor and non-motor neurological symptoms. Most PD cases are idiopathic, no cure available. Recently, it has been proposed that insulin resistance (IR) could be central factor in development. IR associated with neuropathological features like α-synuclein aggregation, loss, neuroinflammation, mitochondrial dysfunction, autophagy. These related impaired metabolism, death, aggravation Moreover, pharmacological options involve signaling improvement non-dopaminergic strategies have under drugs prevent metabolic pathways involved damage. All these approaches improve outcomes. Also, new biomarker identification may allow for an earlier diagnosis high-risk individuals. review describes main implicated development involving IR. presents several therapeutic directed at used treatment. The understanding molecular mechanisms neurodegenerative enhance diagnosis.

Язык: Английский

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Brain-enriched miR-128: Reduced in exosomes from Parkinson’s patient plasma, improves synaptic integrity, and prevents 6-OHDA mediated neuronal apoptosis

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 16

Опубликована: Янв. 12, 2023

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the death of mid-brain dopaminergic neurons. Unfortunately, no effective cure or diagnostic biomarkers for PD are available yet. To address this, present study focuses on brain-enriched small non-coding regulatory RNAs called microRNAs (miRNAs) that released into circulation packaged inside extracellular vesicles exosomes. We collected blood samples from patients and isolated exosomes plasma. qPCR-based detection revealed particular neuron-enriched miR-128 to be significantly decreased in patient-derived Interestingly, concomitant expression was observed cellular models PD. Fluorescent live cell imaging flow-cytometry over-expression can prevent 6-OHDA-mediated mitochondrial superoxide production induction neuronal respectively. This neuroprotective effect found induced by miR-128-mediated inhibition FoxO3a activation, transcription factor involved apoptosis. also resulted down-regulation pro-apoptotic targets- FasL PUMA, at both transcript protein levels. Further downstream, inhibited activation caspases-8, -9 -3, preventing intrinsic extrinsic pathways Additionally, over prevented synaptic proteins- Synaptophysin PSD-95 attenuated neurite shortening, thereby maintaining overall integrity. Thus, our depicts intracellular role apoptosis neurodegeneration its implications as biomarker being detectable circulating patient blood. characterization such exosomal miRNAs hold promise diagnosis

Язык: Английский

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Glial senescence enhances α-synuclein pathology owing to its insufficient clearance caused by autophagy dysfunction

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Янв. 26, 2024

Parkinson's disease (PD) is characterized by the pathological accumulation of α-synuclein (α-syn) and loss dopaminergic neurons in substantia nigra. Aging a significant risk factor for PD. The senescent glial cells aged brain contributes to PD progression inducing chronic neuroinflammatory processes. However, although insufficient degradation α-syn aggregates results deterioration, possible alteration ability clearance glia has received little attention. In this study, we investigated how aging senescence affect capacity clearance. We found that following intra-striatal injection human (hu-α-syn) preformed fibril, hu-α-syn pathology persisted more mice compared with younger microglia exhibited greater than microglia. Moreover, vitro assay revealed was primarily dependent on autophagy-lysosome system rather ubiquitin-proteasome diminished because dysfunction. Overall, study provides new insights into role pathogenesis.

Язык: Английский

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Retinal Alterations Predict Early Prodromal Signs of Neurodegenerative Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1689 - 1689

Опубликована: Янв. 30, 2024

Neurodegenerative diseases are an increasingly common group of that occur late in life with a significant impact on personal, family, and economic life. Among these, Alzheimer’s disease (AD) Parkinson’s (PD) the major disorders lead to mild severe cognitive physical impairment dementia. Interestingly, those may show onset prodromal symptoms early after middle age. Commonly, evaluation these neurodegenerative is based detection biomarkers, where functional structural magnetic resonance imaging (MRI) have shown central role revealing or phases, although it can be expensive, time-consuming, not always available. The aforementioned visual system due pathophysiological mechanisms shared between eye brain. In disease, α-synuclein deposition retinal cells, as well dopaminergic neurons substantia nigra, alters cortex function, resulting modifications field. Similarly, modified by neurofibrillary tangles neuritic amyloid β plaques typically seen brain, this reflect accumulation biomarkers retina during stages postmortem retinas AD patients. light, ophthalmic neurodegeneration could become cost-effective method for diagnosis diseases, overcoming limitations deep This analysis commonly used practice, interest has risen recent years. review will discuss relationship degeneration, highlighting how represent noninvasive straightforward diseases.

Язык: Английский

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Parkinson’s Disease and Photobiomodulation: Potential for Treatment

Journal of Personalized Medicine, Год журнала: 2024, Номер 14(1), С. 112 - 112

Опубликована: Янв. 19, 2024

Parkinson’s disease is the second most common neurodegenerative and increasing in incidence. The combination of motor non-motor symptoms makes this a devastating for people with their care givers. characterised by mitochondrial dysfunction neuronal death substantia nigra, reduction dopamine, accumulation α-synuclein aggregates neuroinflammation. microbiome–gut–brain axis also important disease, involved spread inflammation aggregated α-synuclein. mainstay treatment dopamine replacement therapy, which can reduce some signs. There need additional options to supplement available medications. Photobiomodulation (PBM) form light therapy that has been shown have multiple clinical benefits due its enhancement electron transport chain subsequent increase membrane potential ATP production. PBM modulates cellular signalling inflammation. Clinically, used decades improve wound healing, treat pain, swelling heal deep tissues. Pre-clinical experiments indicated signs provide neuroprotection. This effect seen whether directed head animal or other parts body (remotely). A small number trials given weight possibility using both may potentially slow progression.

Язык: Английский

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Teaghrelin protected dopaminergic neurons in MPTP‐induced Parkinson's disease animal model by promoting PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC1‐α‐mediated mitochondrial biogenesis

Environmental Toxicology, Год журнала: 2024, Номер 39(7), С. 4022 - 4034

Опубликована: Апрель 15, 2024

Abstract Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play significant role pathologic development progression the disease. Teaghrelin, unique bioactive compound some oolong tea varieties, has been demonstrated protect SH‐SY5Y cells against 1‐methyl‐4‐phenylpyridinium induced neurotoxicity by binding ghrelin receptor activate AMPK/SIRT1/PGC‐1α pathway. In this study, an animal model was established using neurotoxin, 1‐methyl‐4phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), byproduct prohibited drug, evaluate oral efficacy teaghrelin on PD monitoring motor dysfunction mice open field, pole, bean walking tests. The results showed that MPTP‐induced significantly attenuated supplementation. Tyrosine hydroxylase dopamine transporter protein were found reduced striatum midbrain MPTP‐treated mice, mitigated Furthermore, administration enhanced mitophagy mitochondria biogenesis, which maintained cell homeostasis prevented accumulation αSyn apoptosis‐related proteins. It seemed protected dopaminergic neurons increasing PINK1/Parkin‐mediated AMPK/SIRT1/PGC‐1α‐mediated highlighting its potential therapeutic maintaining function PD.

Язык: Английский

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