Involvement of Mitochondria in Parkinson’s Disease DOI Open Access
Chi‐Jing Choong, Hideki Mochizuki

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(23), С. 17027 - 17027

Опубликована: Дек. 1, 2023

Mitochondrial dysregulation, such as mitochondrial complex I deficiency, increased oxidative stress, perturbation of dynamics and mitophagy, has long been implicated in the pathogenesis PD. Initiating from observation that toxins cause PD-like symptoms DNA mutations are associated with risk PD, many mutated genes linked to familial forms including PRKN, PINK1, DJ-1 SNCA, have also found affect features. Recent research uncovered a much more involvement mitochondria Disruption quality control coupled abnormal secretion contents dispose damaged organelles may play role Furthermore, due its bacterial ancestry, circulating DNAs can function damage-associated molecular patterns eliciting inflammatory response. In this review, we summarize discuss connection between dysfunction highlighting triggers disease process, intra- extracellular roles PD well therapeutic potential transplantation.

Язык: Английский

Targeting mitophagy in neurodegenerative diseases DOI
Odetta Antico, Paul Thompson, Nicholas T. Hertz

и другие.

Nature Reviews Drug Discovery, Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Язык: Английский

Процитировано

6
Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease DOI Creative Commons
Yumin Wang, Luyan Gao, Jichao Chen

и другие.

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Ноя. 23, 2021

Parkinson’s disease (PD) is a complex neurodegenerative disorder featuring both motor and nonmotor symptoms associated with progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress (OS) has been implicated pathogenesis PD. Genetic environmental factors can produce OS, which as core contributor to initiation progression PD through degeneration neurons. The transcription factor nuclear erythroid 2-related 2 (Nrf2) orchestrates activation multiple protective genes, including heme oxygenase-1 (HO-1), protects cells from OS. Nrf2 also shown exert anti-inflammatory effects modulate mitochondrial function biogenesis. Recently, series studies have reported that different bioactive compounds were be able activate Nrf2/antioxidant response element (ARE) ameliorate PD-associated neurotoxin, animal models tissue culture. In this review, we briefly overview sources OS association between Then, provided concise Nrf2/ARE pathway delineated role played by Nrf2/HO-1 At last, expand our discussion neuroprotective pharmacological modulation potential application activators for treatment This review suggests signaling therapeutic target

Язык: Английский

Процитировано

75
Mitochondrial Sirtuins in Parkinson’s Disease DOI
Ling He, Jihong Wang,

Yazhi Yang

и другие.

Neurochemical Research, Год журнала: 2022, Номер 47(6), С. 1491 - 1502

Опубликована: Фев. 26, 2022

Язык: Английский

Процитировано

40
Primary cilia and SHH signaling impairments in human and mouse models of Parkinson’s disease DOI Creative Commons
Sebastian Schmidt, Malte D. Luecken, Dietrich Trümbach

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 16, 2022

Parkinson's disease (PD) as a progressive neurodegenerative disorder arises from multiple genetic and environmental factors. However, underlying pathological mechanisms remain poorly understood. Using multiplexed single-cell transcriptomics, we analyze human neural precursor cells (hNPCs) sporadic PD (sPD) patients. Alterations in gene expression appear pathways related to primary cilia (PC). Accordingly, these hiPSC-derived hNPCs neurons, observe shortening of PC. Additionally, detect PC PINK1-deficient cellular mouse models familial PD. Furthermore, sPD models, the is accompanied by increased Sonic Hedgehog (SHH) signal transduction. Inhibition this pathway rescues alterations morphology mitochondrial dysfunction. Thus, SHH activity due ciliary dysfunction may be required for development pathoetiological phenotypes observed like Inhibiting overactive signaling potential neuroprotective therapy sPD.

Язык: Английский

Процитировано

38
Mitochondria in Aging and Alzheimer’s Disease: Focus on Mitophagy DOI
Jangampalli Adi Pradeepkiran,

Javaria Baig,

Ann Seman

и другие.

The Neuroscientist, Год журнала: 2023, Номер 30(4), С. 440 - 457

Опубликована: Янв. 3, 2023

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid β and phosphorylated τ protein aggregates in brain, which leads to loss neurons. Under microscope, function mitochondria uniquely primed play a pivotal role neuronal cell survival, energy metabolism, death. Research studies indicate that mitochondrial dysfunction, excessive oxidative damage, defective mitophagy neurons are early indicators AD. This review article summarizes latest development AD: 1) mechanism pathways, 2) importance functions, 3) metabolic pathways 4) link between dysfunction mechanisms AD, 5) potential mitochondrial-targeted therapeutics interventions treat patients with

Язык: Английский

Процитировано

29
Mitochondrial dysfunction in chronic neuroinflammatory diseases (Review) DOI Creative Commons
Pei Qin,

Ye Sun,

Liya Li

и другие.

International Journal of Molecular Medicine, Год журнала: 2024, Номер 53(5)

Опубликована: Апрель 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

Язык: Английский

Процитировано

15
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 DOI
Cian‐Fen Jhuo, Chun‐Jung Chen, Jason T. C. Tzen

и другие.

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

Процитировано

11
Exploring the Prospective Role of Propolis in Modifying Aging Hallmarks DOI Creative Commons
Carla A. Scorza, V Gonçalves, Josef Finsterer

и другие.

Cells, Год журнала: 2024, Номер 13(5), С. 390 - 390

Опубликована: Фев. 24, 2024

Aging populations worldwide are placing age-related diseases at the forefront of research agenda. The therapeutic potential natural substances, especially propolis and its components, has led to these products being promising agents for alleviating several cellular molecular-level changes associated with diseases. With this in mind, scientists have introduced a contextual framework guide future aging research, called hallmarks aging. This encompasses various mechanisms including genomic instability, epigenetic changes, mitochondrial dysfunction, inflammation, impaired nutrient sensing, altered intercellular communication. Propolis, rich array bioactive compounds, functions as potent functional food, modulating metabolism, gut microbiota, immune response, offering significant health benefits. Studies emphasize propolis' properties, such antitumor, cardioprotective, neuroprotective effects, well ability mitigate oxidative stress, DNA damage, pathogenic bacteria growth. article underscores current scientific evidence supporting role controlling molecular characteristics linked hallmarks, hypothesizing geroscience research. aim is discover novel strategies improve quality life older individuals, addressing existing deficits perspectives area.

Язык: Английский

Процитировано

9
Ameliorating Mitochondrial Dysfunction for the Therapy of Parkinson's Disease DOI
Qing Yin Zheng, Hanghang Liu, Yifan Gao

и другие.

Small, Год журнала: 2024, Номер 20(29)

Опубликована: Фев. 22, 2024

Parkinson's disease (PD) is currently the second most incurable central neurodegenerative resulting from various pathogenesis. As "energy factory" of cells, mitochondria play an extremely important role in supporting neuronal signal transmission and other physiological activities. Mitochondrial dysfunction can cause accelerate occurrence progression PD. How to effectively prevent suppress mitochondrial disorders a key strategy for treatment PD root. Therefore, emerging mitochondria-targeted therapy has attracted considerable interest. Herein, relationship between PD, causes results dysfunction, major strategies ameliorating treat are systematically reviewed. The study also prospects main challenges

Язык: Английский

Процитировано

8
Urolithin A protects dopaminergic neurons in experimental models of Parkinson's disease by promoting mitochondrial biogenesis through the SIRT1/PGC-1α signaling pathway DOI
Jia Liu, Jingjing Jiang,

Jingru Qiu

и другие.

Food & Function, Год журнала: 2021, Номер 13(1), С. 375 - 385

Опубликована: Ноя. 23, 2021

Mitochondrial dysfunction contributes to the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). Therapeutic strategies targeting mitochondrial hold considerable promise for treatment PD. Recent reports have highlighted protective role urolithin A (UA), a gut metabolite produced from ellagic acid-containing foods pomegranates, berries and walnuts, in several neurological disorders including Alzheimer's ischemic stroke. However, potential UA PD has not been characterized. In this study, we investigated underlying mechanisms 6-OHDA-induced neurotoxicity cell cultures mice model Our results revealed that protected against 6-OHDA cytotoxicity apoptosis PC12 cells. Meanwhile, administration lesioned ameliorated both motor deficits nigral-striatal dopaminergic neurotoxicity. More important, significantly attenuated cells accompanied by enhanced biogenesis. Mechanistically, demonstrated exerts neuroprotective effects promoting biogenesis via SIRT1-PGC-1α signaling pathway. Taken together, these data provide new insights into novel regulating suggest may therapeutic applications

Язык: Английский

Процитировано

43