Polypharmacological drug design opportunities against Parkinson's disease DOI Creative Commons
Ezra Michelet García Romero, Edgar López‐López, Catalina Soriano‐Correa

et al.

F1000Research, Journal Year: 2022, Volume and Issue: 11, P. 1176 - 1176

Published: Oct. 17, 2022

Background: Parkinson's disease is an attractive model to extend research towards a better understanding of the interrelationship between genes and environment (exposome) therefore ideal for polypharmacological approach due its clinical heterogeneity. Methods: In this paper, we present series chemical scaffolds extracted from ChEMBL 30 Database, with two or more targets PD-related proteins obtained through chemoinformatics methods. This way, describe first adaptation Dual Activity Difference (DAD) map that allows direct identification "dual activity cliffs". Results: We identified 25 antiparkinson small molecules whose pharmacological are directed dopaminergic muscarinic acetyl choline M1-M5 receptors; 2 three norepinephrine transporter, D1-D2 6 both transporter receptors 1 adenosine A2a Dopamine D1-D5 receptors. Conclusion: Chemoinformatics methods 36 related disease. Demonstrating design drugs opportunity in PD.

Language: Английский

Misfolding and aggregation in neurodegenerative diseases: protein quality control machinery as potential therapeutic clearance pathways DOI Creative Commons
Oliwia Koszła, Przemysław Sołek

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 30, 2024

The primary challenge in today's world of neuroscience is the search for new therapeutic possibilities neurodegenerative disease. Central to these disorders lies among other factors, aberrant folding, aggregation, and accumulation proteins, resulting formation toxic entities that contribute neuronal degeneration. This review concentrates on key proteins such as β-amyloid (Aβ), tau, α-synuclein, elucidating intricate molecular events underlying their misfolding aggregation. We critically evaluate mechanisms governing elimination misfolded shedding light potential strategies. specifically examine pathways endoplasmic reticulum (ER) unfolded protein response (UPR), chaperones, chaperone-mediated autophagy (CMA), intersecting signaling Keap1-Nrf2-ARE, along with connected through p62. Above all, we emphasize significance quality control mechanisms, encompassing interventions targeting regulation post-translational modifications, enhancement chaperones clearance. Additionally, focus current new, multi-target approaches. In conclusion, this systematically consolidates insights into emerging strategies predicated aggregates

Language: Английский

Citations

17
Experimental and computational assessment of Antiparkinson Medication effects on meiofauna: Case study of Benserazide and Trihexyphenidyl DOI
Sahar Ishak, Mohamed Allouche,

Ghadah S Alotaibi

et al.

Marine Pollution Bulletin, Journal Year: 2024, Volume and Issue: 205, P. 116668 - 116668

Published: July 6, 2024

Language: Английский

Citations

11
Traditional Chinese exercises for the treatment of neuropsychiatric symptoms in Parkinson’s Disease: A systematic review and meta-analysis DOI Creative Commons
Weiqiang Tan,

Zhaoquan Pan,

Jiawei He

et al.

Complementary Therapies in Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 103134 - 103134

Published: Jan. 1, 2025

Language: Английский

Citations

1
Parkinson’s Disease: Advances in Treatment and the Syntheses of Various Classes of Pharmaceutical Drug Substances DOI
David R. Hill,

Alexander D. Huters,

Timothy B. Towne

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(23), P. 13693 - 13712

Published: Nov. 17, 2023

An overview of Parkinson's disease (PD) prevalence, diagnosis, and currently available treatment options is provided. A comprehensive list different classes marketed pharmaceutical drug products the syntheses various substances are summarized based on published literature.

Language: Английский

Citations

21
Redox Homeostasis, Gut Microbiota, and Epigenetics in Neurodegenerative Diseases: A Systematic Review DOI Creative Commons
Constantin Munteanu, Anca‐Irina Galaction, Marius Turnea

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(9), P. 1062 - 1062

Published: Aug. 30, 2024

Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration structure and function nervous system. These conditions, including Parkinson's disease (PD), Alzheimer's (AD), Huntington's (HD), Amyotrophic lateral sclerosis (ALS), Multiple (MS), often lead to severe cognitive motor deficits. A critical component neurodegenerative pathologies is imbalance between pro-oxidant antioxidant mechanisms, culminating in oxidative stress. The brain's high oxygen consumption lipid-rich environment make it particularly vulnerable damage. Pro-oxidants such as reactive nitrogen species (RNS) (ROS) are continuously generated during normal metabolism, counteracted enzymatic non-enzymatic defenses. In diseases, this balance disrupted, leading neuronal This systematic review explores roles stress, gut microbiota, epigenetic modifications aiming elucidate interplay these factors identify potential therapeutic strategies. We conducted comprehensive search articles published 2024 across major databases, focusing on studies examining relationships redox homeostasis, changes neurodegeneration. total 161 were included, comprising clinical trials, observational studies, experimental research. Our findings reveal that stress plays central role pathogenesis with microbiota composition significantly influencing balance. Specific bacterial taxa markers identified modulators suggesting novel avenues for intervention. Moreover, recent evidence from human animal supports emerging concept targeting homeostasis through therapies. Future research should focus validating targets settings exploring personalized medicine strategies based individual profiles.

Language: Английский

Citations

5
Effect of hyperbaric oxygen therapy for non-motor symptoms among patients with Parkinson's disease: A systematic review and meta-analysis DOI

Zhaoquan Pan,

Weiqiang Tan, Xianhui Ran

et al.

Clinical Rehabilitation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Objective To systematically evaluate the efficacy of hyperbaric oxygen therapy for non-motor symptoms in patients with Parkinson's disease. Data sources A systematic search was performed across several databases, including Chinese Science and Technology Periodical Database, Web Science, SinoMed, PubMed, Cochrane Library, Embase Wanfang databases up to 1 December 2024. Studies considered inclusion comprised randomised controlled trials pre–post control studies. Review methods The authors conducted data extraction literature screening procedures independently. selected studies’ quality evaluated using risk bias technique. Manager 5.3 used conduct meta-analyses, while Stata 15.0 utilised sensitivity analysis assess publication bias. Results Sixteen studies a total 1324 individuals satisfied criteria. results meta-analysis showed that significantly improved scores on Hamilton Anxiety Scale Depression compared baseline (both p < 0.05). Additionally, improvements were observed Montreal Cognitive Assessment, Mini-Mental State Examination, Disease Sleep Scale, Pittsburgh Quality Index, Kubota's Drinking Water Test Unified Rating III. Improvements sleep efficiency extension time also noted controls (all Conclusion findings indicate effectively alleviates such as anxiety, depression, cognitive impairments, disturbances, swallowing dysfunction, well improving motor function disease patients. Since protocol had significant differences between studies, further prospective rigorous methodology are needed.

Language: Английский

Citations

0
Future Perspectives of NMDAR in CNS Disorders DOI Creative Commons
Toni Capó, Joan Biel Rebassa, Iu Raïch

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 877 - 877

Published: Feb. 14, 2025

Neurodegenerative diseases such as Alzheimer's and Parkinson's are among the leading causes of physical cognitive disability across globe. Fifty million people worldwide suffer these diseases, that number is expected to rise population ages. Ictus another pathology also courses with neurodegeneration a cause mortality long-term in developed countries. Schizophrenia not common other mental disorders, affecting approximately 24 worldwide. All disorders have still there an effective pharmacological treatment cure them. The N-methyl-D-aspartate (NMDA) receptor (NMDAR) has attracted attention potential therapeutic target due its important role learning memory implication excitotoxicity processes. Some drugs targeting NMDARs already being used treat symptoms central nervous system (CNS). Here, we aim review implications NMDAR CNS pathologies, target, future perspectives for developing new treatments focused on receptors.

Language: Английский

Citations

0
Slightly viscous oxidized alginate dispersions as vehicles for intranasal administration of the α-synuclein aggregation inhibitor Anle 138b in free form or encapsulated in solid lipid nanoparticles DOI
Rosanna Mallamaci, Stefano Castellani, Limosani Francesca

et al.

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 673, P. 125399 - 125399

Published: Feb. 23, 2025

Language: Английский

Citations

0
Proteome‐Wide Association Study for Finding Druggable Targets in Progression and Onset of Parkinson's Disease DOI Creative Commons
Chenhao Gao,

Haobin Zhou,

Wenpeng Liang

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

To identify and validate causal protein targets that may serve as potential therapeutic interventions for both the onset progression of Parkinson's disease (PD) through integrative proteomic genetic analyses. We utilized large-scale plasma brain quantitative trait loci (pQTL) datasets from deCODE Health study Religious Orders Study/Rush Memory Aging Project (ROS/MAP), respectively. Proteome-wide association studies (PWAS) were conducted using OTTERS framework proteins FUSION tool proteins, examining associations with PD three phenotypes: composite, motor, cognitive. Significant (FDR-corrected p < 0.05) PWAS further validated summary-based Mendelian randomization (SMR), colocalization analyses, reverse (MR) to establish causality. Phenome-wide (PheW-MR) was performed assess side effects across 679 traits when targeting these reduce PD-related phenotype risk by 20%. Additionally, we cellular distribution-based clustering gene expression data Allen Brain Atlas (ABA) explore distribution key regions, constructed protein-protein interaction (PPI) networks via STRING database interactions among evaluated druggability identified DrugBank opportunities drug repurposing. Our analyses 25 candidate associated phenotypes, including 16 linked (10 cognitive, 4 3 composite) 9 onset. Notably, GPNMB implicated in tissues PheW-MR revealed predominantly beneficial targets, 83.7% indicating positive outcomes 16.3% adverse effects. Cellular categorized into distinct profiles cell types ABA. PPI network analysis highlighted one cluster cognitive Druggability assessment 15 out had repurposing treatment. have PD, providing new insights research development treatment strategies PD.

Language: Английский

Citations

0
Current amyloid inhibitors: therapeutic applications and nanomaterial-based innovations DOI
Paula López-García,

María M. Tejero-Ojeda,

Marisela Morales

et al.

Progress in Neurobiology, Journal Year: 2025, Volume and Issue: unknown, P. 102734 - 102734

Published: Feb. 1, 2025

Language: Английский

Citations

0