New perspectives on the role of mitochondria in Parkinson's disease DOI Creative Commons
Shiyi Yin, Yongjiang Zhang, Jiannan Wu

et al.

Journal of Neurorestoratology, Journal Year: 2024, Volume and Issue: 12(2), P. 100112 - 100112

Published: March 16, 2024

Mitochondrial dysfunction is pivotal in the occurrence and development of Parkinson's disease (PD). Interventions to increase mitochondrial biogenesis maintain balance turnover have potential protect against neurological damage. In addition their crucial role tricarboxylic acid cycle, mitochondria impact diverse activities, including cellular metabolism, quality control, production reactive oxygen species. Thus, it has become imperative better understand regulation function PD. With this review, we aim stimulate research that explores mitochondria-oriented neuroprotection strategies turnover. First, summarize on newly discovered genes regulate PD autophagy through PTEN-induced kinase 1 (PINK1), namely AMBRA1, SYNJ2BP, SIAH3. Second, review PD-related proteins, STRT3 SIRT6, unfolded protein response, covering mechanisms involvement Third, emphasize roles complex, pyroptosis, copper-induced cell death damage Finally, present a brief overview new therapeutic correct defects may be applicable for targeting patients.

Language: Английский

Ferroptosis in Parkinson's disease: Molecular mechanisms and therapeutic potential DOI

Xv-shen Ding,

Li Gao, Han Zheng

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102077 - 102077

Published: Sept. 24, 2023

Language: Английский

Citations

74
Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects DOI Creative Commons

Qin Ru,

Yusheng Li,

Lin Chen

et al.

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

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

Citations

64
The Role of Calcium and Iron Homeostasis in Parkinson’s Disease DOI Creative Commons
Ji Wang, Jindong Zhao, Kunying Zhao

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(1), P. 88 - 88

Published: Jan. 17, 2024

Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis calcium causes cell dysfunction or even death. PD (Parkinson’s disease) is the second most common neurological disorder in humans, for which there currently no viable treatment options effective strategies cure delay progression. Pathological hallmarks PD, such as dopaminergic neuronal death intracellular α-synuclein deposition, closely involved perturbations accumulation. Here, we summarize mechanisms by Ca2+ signaling influences promotes progression main ferroptosis Parkinson’s disease. Understanding imbalances contribute this disease critical developing treatments combat devastating disorder.

Language: Английский

Citations

15
Canonical and noncanonical autophagy: involvement in Parkinson’s disease DOI Creative Commons
Maria Sakurai, Tomoki Kuwahara

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 30, 2025

Autophagy is the major degradation process in cells and involved a variety of physiological pathological functions. While macroautophagy, which employs series molecular cascades to form ATG8-coated double membrane autophagosomes for degradation, remains well-known type canonical autophagy, microautophagy chaperon-mediated autophagy have also been characterized. On other hand, recent studies focused on functions proteins beyond intracellular including noncanonical known as conjugation ATG8 single membranes (CASM), autophagy-related extracellular secretion. In particular, CASM unique that it does not require upstream mechanisms, while system manner different from autophagy. There many reports involvement these mechanisms neurodegenerative diseases, with Parkinson’s disease (PD) receiving particular attention because important roles several causative risk genes, LRRK2. this review, we will summarize discuss contributions cellular functions, special focus pathogenesis PD.

Language: Английский

Citations

2
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances DOI Creative Commons
Qiu Jiang, Jie Liu, Shan Huang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 10, 2025

Abstract In the context of global ageing, prevalence neurodegenerative diseases and dementia, such as Alzheimer’s disease (AD), is increasing. However, current symptomatic disease-modifying therapies have achieved limited benefits for in clinical settings. Halting progress neurodegeneration cognitive decline or even improving impaired cognition function are clinically meaningful goals treatments diseases. Ageing primary risk factor their associated comorbidities, vascular pathologies, elderly individuals. Thus, we aim to elucidate role ageing from perspective a complex system, which brain core peripheral organs tissues form holistic network support functions. During progressive deterioration structure entire body hampers its active adaptive responses various stimuli, thereby rendering individuals more vulnerable Consequently, propose that prevention treatment should be grounded antiageing rejuvenation means complemented by interventions targeting disease-specific pathogenic events. This integrated approach promising strategy effectively prevent, pause slow down progression

Language: Английский

Citations

1
NOX4 exacerbates Parkinson’s disease pathology by promoting neuronal ferroptosis and neuroinflammation DOI Creative Commons
Zhihao Lin,

Chang-Zhou Ying,

Xiaoli Si

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(7), P. 2038 - 2052

Published: July 10, 2024

JOURNAL/nrgr/04.03/01300535-202507000-00026/figure1/v/2024-09-09T124005Z/r/image-tiff Parkinson’s disease is primarily caused by the loss of dopaminergic neurons in substantia nigra compacta. Ferroptosis, a novel form regulated cell death characterized iron accumulation and lipid peroxidation, plays vital role neurons. However, molecular mechanisms underlying ferroptosis have not yet been completely elucidated. NADPH oxidase 4 related to oxidative stress, however, whether it regulates neuronal remains unknown. The aim this study was determine involved ferroptosis, if so, what mechanism. We found that transcriptional regulator activating transcription factor 3 increased expression astrocytes an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced model. inhibition improved behavioral impairments observed model animals reduced Moreover, peroxidation animals. Mechanistically, we interacted with activated protein kinase C α prevent Furthermore, lowering astrocytic lipocalin-2 expression, neuroinflammation. These findings demonstrate promotes neuroinflammation, which contribute neuron death, suggesting possible therapeutic target for disease.

Language: Английский

Citations

7
Role of the globus pallidus in motor and non-motor symptoms of Parkinson’s disease DOI Creative Commons

Yi‐Miao Jiang,

Zengxin Qi,

Hui‐Xian Zhu

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(6), P. 1628 - 1643

Published: June 3, 2024

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells substantia nigra, which leads to dopamine deficiency brain that subsequently manifests as various motor and non-motor symptoms. This review aims summarize involvement both manifestations disease. firing activities parvalbumin neurons medial pallidus, including rate pattern, exhibit strong correlations with bradykinesia rigidity associated Increased beta oscillations, are highly correlated rigidity, regulated lateral pallidus. Furthermore, strongly linked loss dopaminergic projections within cortical-basal ganglia-thalamocortical loop. Resting tremors attributed transmission pathological signals from through cortex cerebellum-ventral intermediate nucleus cortico-striato-pallidal loop responsible for mediating pallidi-associated sleep disorders. Medication deep stimulation primary therapeutic strategies addressing treatment symptoms early stages disease, while has been clinically proven be effective alleviating patients advanced particularly movement disorders caused levodopa. Deep targeting internus can improve function tremor-dominant non-tremor-dominant externus alter temporal pattern neural activity throughout ganglia-thalamus network. Therefore, composition neurons, neurotransmitters act on them, their electrical activity, circuits they form guide search new multi-target drugs treat clinical practice. Examining potential intra-nuclear circuit mechanisms facilitate management minimizing side effects stimulation.

Language: Английский

Citations

4
Ferroptosis: a novel pathogenesis and therapeutic strategies for Parkinson disease: A review DOI Creative Commons

Di Jiao,

Yang Yang, Kejing Wang

et al.

Medicine, Journal Year: 2025, Volume and Issue: 104(3), P. e41218 - e41218

Published: Jan. 17, 2025

Parkinson disease (PD) is the second most common neurodegenerative disease, and its incidence climbing every year, but there still a lack of effective clinical treatments. In recent years, many studies have shown that ferroptosis plays key role in progression PD. Most importantly, cellular animal trials episodes PD can be alleviated by inhibiting process, such as utilizing inhibitors, chelating agents, others. Here, we review ferroptosis, new form cell death, pathogenesis PD, summarize therapeutic strategies for targeting hoping to provide thinking study development strategies.

Language: Английский

Citations

0
Rhamnetin‐3‐O‐α‐L‐Rhamnoside Attenuates Alcoholic Liver Injury in Mice via Regulation of the Autophagy/Ferroptosis Pathway DOI Creative Commons
Jiangtao Zhou, Binghao Zhao, Fan Yang

et al.

Journal of Food Biochemistry, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Rhamnetin‐3‐α‐L‐rhamnoside (ARR) is the principal monomer isolated from Loranthus tanakae Franch . and Sav, with effect of prevention treatment inflammatory diseases. This study was to investigate effects ARR on acute alcoholic liver injury (ALI) in a mouse model elucidate mechanisms. Methods: Balb/c mice were divided into six groups: naive control (NC), (MC), positive (PC), low‐dose group (ARR‐L), medium‐dose (ARR‐M), high‐dose (ARR‐H). The lasted for 11 days, alcohol administration 9th 11th day. Blood samples taken 24 h postadministration glutamic pyruvic transaminase (ALT) oxaloacetic (AST) detection. Liver tissue underwent hematoxylin–eosin (H&E) staining, immunohistochemical analysis, biochemical assays glutathione (GSH), (MDA), superoxide dismutase (SOD), iron. Western blotting analysis conducted ferroptosis‐related proteins including peroxidase 4 (GPX4), solute carrier family 7 member (SLC7A11), ferritin light chain (FTL) as well autophagy‐related comprising benzyl chloride 1 (Beclin‐1), autophagy‐associated Gene 5 (ATG5), sequestosome (P62), microtubule associated protein 3 (LC3). Results: H&E staining showed that caused cell damage, which improved groups. indicated decreased levels heme oxygenase (HO‐1) nuclear factor erythroid 2–related 2 (Nrf2) MC mice, whereas enhanced index, serum ALT, AST significantly elevated group, confirm successful modeling. Both drug ameliorated aminotransferase levels, oxidative stress, Furthermore, western revealed abnormal expression ferroptosis‐ due alcohol. In comparison groups increased expressions GPX4, SLC7A11, Beclin‐1, ATG5, LC3II/I FTL P62. Conclusion: prevents ALI by inhibiting ferroptosis inducing autophagy. These findings suggested may represent natural therapeutic approach this disease.

Language: Английский

Citations

0
ROS Regulate Rotenone-induced SH-SY5Y Dopamine Neuron Death Through Ferroptosis-mediated Autophagy and Apoptosis DOI
Xinying Li, Weiran Li, Xiaoliang Xie

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Language: Английский

Citations

0