Cellular mitophagy: Mechanism, roles in diseases and small molecule pharmacological regulation

Theranostics, Journal Year: 2023, Volume and Issue: 13(2), P. 736 - 766

Published: Jan. 1, 2023

Cellular mitophagy means that cells selectively wrap and degrade damaged mitochondria through an autophagy mechanism, thus maintaining intracellular homeostasis.In recent years, has received increasing attention as a research hotspot related to the pathogenesis of clinical diseases, such neurodegenerative cardiovascular cancer, metabolic so on.It been found regulation may become new direction for treatment some diseases.In addition, numerous small molecule modulators have also reported, which provides opportunities comprehend procedure potential therapeutic development.Taken together, in this review, we summarize current understanding mechanism mitophagy, discuss roles its relationship with introduce existing small-molecule pharmacological further highlight significance their development.

Language: Английский

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Genetics and Pathogenesis of Parkinson's Syndrome

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2022, Volume and Issue: 18(1), P. 95 - 121

Published: Sept. 13, 2022

Parkinson's disease (PD) is clinically, pathologically, and genetically heterogeneous, resisting distillation to a single, cohesive disorder. Instead, each affected individual develops virtually unique form of syndrome. Clinical manifestations consist variable motor nonmotor features, myriad overlaps are recognized with other neurodegenerative conditions. Although most commonly characterized by alpha-synuclein protein pathology throughout the central peripheral nervous systems, distribution varies pathologies modify PD or trigger similar manifestations. Nearly all influenced. More than 100 genes genetic loci have been identified, cases likely arise from interactions among many common rare variants. Despite its complex architecture, insights experimental dissection coalesce reveal unifying biological themes, including synaptic, lysosomal, mitochondrial, andimmune-mediated mechanisms pathogenesis. This emerging understanding syndrome, coupled advances in biomarkers targeted therapies, presages successful precision medicine strategies.

Language: Английский

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Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 2, 2023

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on backbones amino acid side chains proteins and expand diversity proteins, which provides basis for emergence organismal complexity. To date, more than 650 types protein modifications, such as most well-known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short-chain long-chain acylation redox irreversible have been described, inventory is still increasing. By changing conformation, localization, activity, stability, charges, interactions with other biomolecules, PTMs ultimately alter phenotypes biological processes cells. The homeostasis important human health. Abnormal may cause changes in properties loss functions, are closely related occurrence development various diseases. In this review, we systematically introduce characteristics, regulatory mechanisms, functions health addition, therapeutic prospects diseases by targeting associated enzymes also summarized. This work will deepen understanding promote discovery diagnostic prognostic markers drug targets

Language: Английский

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Apoptosis and its therapeutic implications in neurodegenerative diseases

Clinical Anatomy, Journal Year: 2021, Volume and Issue: 35(1), P. 65 - 78

Published: Sept. 24, 2021

Neurodegenerative disorders are characterized by progressive loss of particular populations neurons. Apoptosis has been implicated in the pathogenesis neurodegenerative diseases, including Parkinson disease, Alzheimer Huntington and amyotrophic lateral sclerosis. In this review, we focus on existing notions relevant to comprehending apoptotic death process, morphological features, mediators regulators cellular apoptosis. We also highlight evidence neuronal Additionally, present potential therapeutic agents that could modify pathway aforementioned diseases delay disease progression. Finally, review clinical trials were conducted evaluate use anti-apoptotic drugs treatment order essential need for early detection intervention humans.

Language: Английский

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Role of dopamine in the pathophysiology of Parkinson’s disease

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: Sept. 18, 2023

A pathological feature of Parkinson's disease (PD) is the progressive loss dopaminergic neurons and decreased dopamine (DA) content in substantia nigra pars compacta PD brains. DA neurotransmitter neurons. Accumulating evidence suggests that interacts with environmental genetic factors to contribute pathophysiology. Disturbances synthesis, storage, transportation metabolism have been shown promote neurodegeneration various models. unstable can undergo oxidation produce multiple reactive toxic by-products, including oxygen species, quinones, 3,4-dihydroxyphenylacetaldehyde. Here we summarize highlight recent discoveries on DA-linked pathophysiologic pathways, discuss potential protective therapeutic strategies mitigate complications associated DA.

Language: Английский

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Mitochondrial dysfunction in neurodegenerative disorders

Neurotherapeutics, Journal Year: 2023, Volume and Issue: 21(1), P. e00292 - e00292

Published: Dec. 19, 2023

Recent advances in understanding the role of mitochondrial dysfunction neurodegenerative diseases have expanded opportunities for neurotherapeutics targeting mitochondria to alleviate symptoms and slow disease progression. In this review, we offer a historical account biology disease. Additionally, summarize current knowledge normal physiology pathogenesis dysfunction, disease, therapeutics recent therapeutic advances, as well future directions function. A focus is placed on reactive oxygen species their disruption telomeres effects epigenome. The etiology progression Alzheimer's amyotrophic lateral sclerosis, Parkinson's Huntington's are discussed depth. Current clinical trials mitochondria-targeting discussed.

Language: Английский

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Mitochondrial Dysfunction in Parkinson’s Disease: From Mechanistic Insights to Therapy

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: June 20, 2022

Parkinson's disease (PD) is one of the most common neurodegenerative movement disorders worldwide. There are currently no cures or preventative treatments for PD. Emerging evidence indicates that mitochondrial dysfunction closely associated with pathogenesis sporadic and familial Because dopaminergic neurons have high energy demand, cells affected by PD exhibit promotes disease-defining loss in substantia nigra pars compacta (SNpc). The mitochondrion has a particularly important role as cellular "powerhouse" neurons. Therefore, mitochondria become promising therapeutic target treatments. This review aims to describe pathology PD, outline genes factors related summarize current knowledge on quality control give an overview strategies targeting neuroprotective interventions

Language: Английский

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A blood-based marker of mitochondrial DNA damage in Parkinson’s disease

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(711)

Published: Aug. 30, 2023

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, and neuroprotective or disease-modifying interventions remain elusive. High-throughput markers aimed at stratifying patients on basis of shared etiology are required to ensure success therapies in clinical trials. Mitochondrial dysfunction plays a prominent role pathogenesis PD. Previously, we found brain region–specific accumulation mitochondrial DNA (mtDNA) damage PD neuronal culture animal models, as well human postmortem tissue. To investigate mtDNA potential blood-based marker for PD, describe herein PCR-based assay (Mito DX ) that allows accurate real-time quantification scalable platform. We was increased peripheral blood mononuclear cells derived from with idiopathic those harboring PD-associated leucine-rich repeat kinase 2 ( LRRK2 G2019S mutation comparison age-matched controls. In addition, elevated non–disease-manifesting carriers, demonstrating can occur irrespective diagnosis. further established Lrrk2 knock-in mice displayed damage, whereas knockout showed fewer lesions ventral midbrain, compared wild-type control mice. Furthermore, small-molecule inhibitor mitigated rotenone rat midbrain neuron model patient–derived lymphoblastoid cell lines. Quantifying using Mito may have utility candidate measuring pharmacodynamic response inhibitors.

Language: Английский

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Epidemiology of Parkinson’s Disease: An Update

Current Neurology and Neuroscience Reports, Journal Year: 2024, Volume and Issue: 24(6), P. 163 - 179

Published: April 20, 2024

Language: Английский

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Mitochondrial dysfunction in chronic neuroinflammatory diseases (Review)

International Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 53(5)

Published: April 2, 2024

Chronic neuroinflammation serves a key role in the onset and progression of neurodegenerative disorders. Mitochondria serve as central regulators neuroinflammation. In addition to providing energy cells, mitochondria also participate immunoinflammatory response disorders including Alzheimer's disease, Parkinson's multiple sclerosis epilepsy, by regulating processes such cell death inflammasome activation. Under inflammatory conditions, mitochondrial oxidative stress, epigenetics, dynamics calcium homeostasis imbalance may underlying regulatory mechanisms for these diseases. Therefore, investigating related dysfunction result therapeutic strategies against chronic neurodegeneration. The present review summarizes neuroinflammatory diseases current treatment approaches that target

Language: Английский

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