Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 187, P. 106314 - 106314

Published: Oct. 1, 2023

Poly (ADP-ribose) polymerase-1 (PARP-1) is the most extensively studied member of PARP superfamily, with its primary function being facilitation DNA damage repair processes. Parthanatos a type regulated cell death cascade initiated by PARP-1 hyperactivation, which involves multiple subroutines, including accumulation ADP-ribose polymers (PAR), binding PAR and apoptosis-inducing factor (AIF), release AIF from mitochondria, translocation AIF/macrophage migration inhibitory (MIF) complex, massive MIF-mediated fragmentation. Over past few decades, role in central nervous system health disease has received increasing attention. In this review, we discuss biological functions neural proliferation differentiation, memory formation, brain ageing, epigenetic regulation. We then elaborate on involvement PARP-1-dependant parthanatos various neuropathological processes, such as oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, autophagy damage, endoplasmic reticulum (ER) stress. Additional highlight contains PARP-1's implications initiation, progression, therapeutic opportunities for different neurological illnesses, neurodegenerative diseases, stroke, autism spectrum disorder (ASD), sclerosis (MS), epilepsy, neuropathic pain (NP). Finally, emerging insights into repurposing inhibitors management diseases are provided. This review aims to summarize exciting advancements critical disorders, may open new avenues options targeting or parthanatos.

Language: Английский

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Role of NLRP3 in Parkinson's disease: Specific activation especially in dopaminergic neurons

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28838 - e28838

Published: March 28, 2024

Parkinson's disease (PD) is a neurodegenerative disorder with motor symptoms like bradykinesia, tremors, and balance issues. The pathology recognized by progressively degenerative nigrostriatal dopaminergic neurons (DANs) loss. Its exact pathogenesis unclear. Numerous studies have shown that nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) contributes to the of PD. Previous demonstrated over-activation NLRP3 inflammasome in microglia indirectly leads loss DANs, which can worsen In recent years, autopsy analyses PD patients models revealed upregulation expression within DANs activation sufficient drive neuronal loss, whereas microglial occurs after death, inhibition intraneuronal prevents degeneration DANs. this review, we provide research evidence related as well focus on possible mechanisms neurons, aiming new way thinking about prevention

Language: Английский

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Treadmill exercise mitigates rotenone-induced neuroinflammation and α-synuclein level in a mouse model of Parkinson’s disease

Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 149540 - 149540

Published: Feb. 1, 2025

Language: Английский

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Olfactory Dysfunction in Parkinson’s Disease, Its Functional and Neuroanatomical Correlates

NeuroSci, Journal Year: 2023, Volume and Issue: 4(2), P. 134 - 151

Published: June 5, 2023

Parkinson's disease (PD) is known for its motor alterations, but the importance of non-motor symptoms (NMSs), such as olfactory dysfunction (OD), increasingly recognized. OD may manifest during prodromal period disease, even before appear. Therefore, it suggested that this symptom could be considered a marker PD. This article briefly describes PD, evolution knowledge about in prevalence NMS and role diagnosis PD progression, assessment olfaction patients with α-synuclein aggregates pathophysiology then some functional, morphological, histological alterations observed different structures related to system, epithelium, bulb, anterior nucleus, tract, piriform cortex, hippocampus, orbitofrontal amygdala. In addition, considering growing evidence suggests cerebellum also involved has been included work. Comprehending existing functional neuroanatomical relevant better understanding mechanisms behind neurodegenerative disorder.

Language: Английский

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Program with last minute abstracts of the Padua Days on Muscle and Mobility Medicine, 27 February – 2 March, 2024 (2024Pdm3)

European Journal of Translational Myology, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 2, 2024

During the 2023 Padua Days on Muscle and Mobility Medicine 2024 meeting was scheduled from 28 February to 2 March (2024Pdm3). autumn program expanded with Scientific Sessions which will take place over five days (in this includes 29), starting afternoon of 27 in Conference Rooms Hotel Petrarca, Thermae Euganean Hills (Padua), Italy. As per consolidated tradition, second day Padua, for occasion Sala San Luca Monastery Santa Giustina Prato della Valle, Confirming attractiveness Medicine, 100 titles were accepted until 15 December (many more than expected), forcing organization parallel sessions both 1 2024. The include lectures oral presentations scientists clinicians Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Denmark, Egypt, France, Germany, Iceland, Ireland, Italy, Romania, Russia, Slovenia, Switzerland, UK USA. Only Australia, China, India Japan are missing edition. But we confident that authors those countries who publish articles PAGEpress: European Journal Translational Myology (EJTM: 2022 ESCI Clarivate's Impact Factor: 2.2; SCOPUS Cite Score: 3.2) decide join us coming years. Together established by 31 January 2024, abstracts circulate during only electronic version EJTM Issue 34 (1) See you soon person at Petrarca Montegrotto Terme, inauguration or on-line free via Zoom. Send your email address if not traditional participants listed Pdm3 books.

Language: Английский

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Interplay of human gastrointestinal microbiota metabolites: Short-chain fatty acids and their correlation with Parkinson’s disease

Medicine, Journal Year: 2024, Volume and Issue: 103(17), P. e37960 - e37960

Published: April 26, 2024

Short-chain fatty acids (SCFAs) are, the metabolic byproducts of intestinal microbiota that, are generated through anaerobic fermentation undigested dietary fibers. SCFAs play a pivotal role in numerous physiological functions within human body, including maintaining mucosal health, modulating immune functions, and regulating energy metabolism. In recent years, extensive research evidence has indicated that significantly involved onset progression Parkinson disease (PD). However, precise mechanisms remain elusive. This review comprehensively summarizes progress understanding how impact PD pathogenesis underlying mechanisms. Primarily, we delve into synthesis, metabolism, signal transduction body. Subsequently, an analysis SCFA levels patients with is presented. Furthermore, expound upon which induce inflammatory responses, oxidative stress, abnormal aggregation alpha-synuclein, intricacies gut-brain axis. Finally, provide critical explore potential therapeutic as promising targets for treating PD.

Language: Английский

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PADG‐Pred: Exploring Ensemble Approaches for Identifying Parkinson's Disease Associated Biomarkers Using Genomic Sequences Analysis

IET Systems Biology, Journal Year: 2025, Volume and Issue: 19(1)

Published: Jan. 1, 2025

ABSTRACT Parkinson's disease (PD), a degenerative disorder affecting the nervous system, manifests as unbalanced movements, stiffness, tremors, and coordination difficulties. Its cause, believed to involve genetic environmental factors, underscores critical need for prompt diagnosis intervention enhance treatment effectiveness. Despite array of available diagnostics, their reliability remains challenge. In this study, an innovative predictor PADG‐Pred is proposed identification associated biomarkers, utilising genomic profile. novel predictor, PADG‐Pred, which not only identifies biomarkers through profiling but also uniquely integrates multiple statistical feature extraction techniques with ensemble‐based classification frameworks, thereby providing more robust interpretable decision‐making process than existing tools. The processed dataset was utilised moments it further involved in extensive training model using diverse techniques, encompassing Ensemble methods; XGBoost, Random Forest, Light Gradient Boosting Machine, Bagging, ExtraTrees, Stacking. State‐of‐the‐art validation procedures are applied, assessing key metrics such specificity, accuracy, sensitivity/recall, Mathew's correlation coefficient. outcomes demonstrate outstanding performance PADG‐RF, showcasing accuracy consistently achieving ∼91% independent set, ∼94% 5‐fold, ∼96% 10‐fold cross‐validation.

Language: Английский

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Transcriptome analysis reveals that the injection of mesenchymal stem cells remodels extracellular matrix and complement components of the brain through PI3K/AKT/FOXO1 signaling pathway in a neuroinflammation mouse model

Genomics, Journal Year: 2025, Volume and Issue: 117(3), P. 111033 - 111033

Published: March 22, 2025

Language: Английский

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α -Lipoic acid alleviates Parkinson’s disease by suppressing S100A9-mediated pyroptosis

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 155, P. 114539 - 114539

Published: April 14, 2025

Language: Английский

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Sex and Brain: The Role of Sex Chromosomes and Hormones in Brain Development and Parkinson’s Disease

Cells, Journal Year: 2023, Volume and Issue: 12(11), P. 1486 - 1486

Published: May 27, 2023

Sex hormones and genes on the sex chromosomes are not only key factors in regulation of sexual differentiation reproduction but they also deeply involved brain homeostasis. Their action is crucial for development brain, which presents different characteristics depending individuals. The role these players fundamental maintenance function during adulthood as well, thus being important with respect to age-related neurodegenerative diseases. In this review, we explore biological analyze its impact predisposition toward progression particular, focus Parkinson’s disease, a disorder that has higher incidence male population. We report how encoded by could protect from disease or alternatively predispose development. finally underline importance considering when studying physiology pathology cellular animal models order better understand etiology develop novel tailored therapeutic strategies.

Language: Английский

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