Animal models of Parkinson’s disease: bridging the gap between disease hallmarks and research questions

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

Published: July 19, 2023

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. More than 200 years after its first clinical description, PD remains serious affliction that affects growing proportion of the population. Prevailing treatments only alleviate symptoms; there still neither cure targets processes nor therapies modify course disease. Over past decades, several animal models have been developed to study PD. Although no model precisely recapitulates pathology, they provide valuable information contributes our understanding limitations treatment options. This review comprehensively summarizes different available for research, with focus on those induced drugs, neurotoxins, pesticides, genetic alterations, α-synuclein inoculation, viral vector injections. We highlight their characteristics ability reproduce PD-like phenotypes. It essential realize strengths weaknesses each induction technique at disposal are determined research question being asked. Our review, therefore, seeks better aid researchers ensuring concrete discernment classical novel in research.

Language: Английский

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The role of tyrosine hydroxylase as a key player in neuromelanin synthesis and the association of neuromelanin with Parkinson’s disease

Journal of Neural Transmission, Journal Year: 2023, Volume and Issue: 130(5), P. 611 - 625

Published: March 20, 2023

Abstract The dark pigment neuromelanin (NM) is abundant in cell bodies of dopamine (DA) neurons the substantia nigra (SN) and norepinephrine (NE) locus coeruleus (LC) human brain. During progression Parkinson’s disease (PD), together with degeneration respective catecholamine (CA) neurons, NM levels SN LC markedly decrease. However, questions remain among others on how associated PD it synthesized. biosynthesis pathway brain has been controversial because presence tyrosinase CA elusive. We propose following synthesis these neurons: (1) Tyrosine converted by tyrosine hydroxylase (TH) to L-3,4-dihydroxyphenylalanine (L-DOPA), which aromatic L-amino acid decarboxylase DA, β-hydroxylase NE; (2) DA or NE autoxidized quinone (DAQ) (NEQ); (3) DAQ NEQ eumelanic (euNM) pheomelanic (pheoNM) absence cysteine, respectively. This process involves proteins as cysteine source iron. also discuss whether amounts per neuromelanin-positive (NM + ) neuron are higher brain, quantitatively correlates neurodegeneration, an active lifestyle may reduce formation.

Language: Английский

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Neuroinflammation in Parkinson’s Disease: From Gene to Clinic: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5792 - 5792

Published: March 17, 2023

Parkinson’s disease is a neurodegenerative whose progression and clinical characteristics have close bidirectional multilevel relationship with the process of neuroinflammation. In this context, it necessary to understand mechanisms involved in neuroinflammation–PD link. This systematic search was, hereby, conducted focus on four levels where alterations associated neuroinflammation PD been described (genetic, cellular, histopathological clinical-behavioral) by consulting PubMed, Google Scholar, Scielo Redalyc engines, including studies, review articles, book chapters case studies. Initially, 585,772 articles were included, and, after applying inclusion exclusion criteria, 84 obtained that contained information about association gene, molecular, tissue neuroanatomical expression as well clinical-behavioral manifestations PD.

Language: Английский

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Recent Advances in Characterization of Melanin Pigments in Biological Samples

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8305 - 8305

Published: May 5, 2023

The melanin pigments eumelanin (EM) and pheomelanin (PM), which are dark brown to black yellow reddish-brown, respectively, widely found among vertebrates. They produced in melanocytes the epidermis, hair follicles, choroid, iris, inner ear, other tissues. diversity of colors animals is mainly caused by quantity quality their melanin, such as ratios EM versus PM. We have developed micro-analytical methods simultaneously measure PM used these study biochemical genetic fundamentals pigmentation. photoreactivity has become a major focus research because postulated relevance for risk UVA-induced melanoma. Our application many clinical studies on conditions associated with alterations Recently, besides chemical degradative methods, been characterization also discussed here.

Language: Английский

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Revolutionizing our understanding of Parkinson’s disease: Dr. Heinz Reichmann’s pioneering research and future research direction

Journal of Neural Transmission, Journal Year: 2024, Volume and Issue: 131(12), P. 1367 - 1387

Published: Aug. 7, 2024

Millions of individuals around the world are afflicted with Parkinson's disease (PD), a prevalent and incapacitating neurodegenerative disorder. Dr. Reichmann, distinguished professor neurologist, has made substantial advancements in domain PD research, encompassing both fundamental scientific investigations practical applications. His research illuminated etiology treatment PD, as well function energy metabolism premotor symptoms. As precursor to number neurotransmitters neuromodulators that implicated pathophysiology he also investigated application tryptophan (Trp) derivatives disease. principal findings insights summarized synthesized this narrative review article, which emphasizes challenges implications for future research. This aims identify analyze key contributions Reichmann field ultimate goal informing directions domain. By examining Reichmann's work, study seeks provide comprehensive understanding his major how they can be applied advance diagnosis PD. paper explores potential intersection emerging avenues, such investigation Trp its metabolites, particularly kynurenines, could lead new therapeutic strategies managing disorders like

Language: Английский

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The biochemistry of melanogenesis: an insight into the function and mechanism of melanogenesis-related proteins

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 20, 2024

Melanin is an amino acid derivative produced by melanocyte through a series of enzymatic reactions using tyrosinase as substrate. Human skin and hair color also closely related to melanin, so understanding the mechanisms proteins that produce melanin very important. There are many involved in process expression, For example, formation such p53, HNF-1α (Hepatocyte nuclear factor 1α), SOX10 (Sry-related HMg-Box gene 10) pax3 (paired box 3), MC1R(Melanocortin 1 Receptor), MITF (Microphthalmia-associated transcription factor), TYR (tyrosinase), TYRP1 (tyrosinase-related protein-1), TYRP2 protein-2), can be regulated changing their content control production rate melanin. Others, OA1 (ocular albinism type 1), Par-2 (protease-activated receptor 2) Mlph (Melanophilin), have been found transfer melanosomes from melanocytes keratinocytes, regulate amount human epidermal depth color. In addition above proteins, there other protein families BLOC, Rab Rho. This article reviews origin melanocytes, affecting basic causes mutations. addition, we summarized active ingredients 5 popular whitening cosmetics action.

Language: Английский

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Advances of curcumin in nervous system diseases: the effect of regulating oxidative stress and clinical studies

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 1, 2024

In recent years, researchers have highly observed that neurological disorders (NSDs) with the aging of population are a global health burden whose prevalence is increasing every year. Previous evidence suggested occurrence correlated predisposing factors such as inflammation, aging, and injury. Particularly, neuronal cells susceptible to oxidative stress, leading lesions caused by high oxygen-consuming properties. Oxidative stress (OS) state peroxidation, which occurs result disruption balance between oxidizing antioxidizing substances. The intermediates free radicals, hydrogen peroxide (H

Language: Английский

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N‐homocysteinylation of DJ‐1 promotes neurodegeneration in Parkinson's disease

Aging Cell, Journal Year: 2024, Volume and Issue: 23(5)

Published: Feb. 21, 2024

DJ-1, also known as Parkinson's disease protein 7 (Park7), is a multifunctional that regulates oxidative stress and mitochondrial function. Dysfunction of DJ-1 implicated in the pathogenesis (PD). Hyperhomocysteinemia associated with an increased risk PD. Here we show homocysteine thiolactone (HTL), reactive thioester (Hcy), covalently modifies on lysine 182 (K182) residue age-dependent manner. The N-homocysteinylation (N-hcy) abolishes its neuroprotective effect against dysfunction, exacerbating cell toxicity. Blocking N-hcy restores protective effect. These results indicate promotes progression Inhibiting may exert

Language: Английский

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Design, synthesis, and molecular dynamics simulation studies of some novel kojic acid fused 2-amino-3-cyano-4H-pyran derivatives as tyrosinase inhibitors

BMC Chemistry, Journal Year: 2024, Volume and Issue: 18(1)

Published: Feb. 22, 2024

Abstract A novel series of kojic acid fused 2-amino-3-cyano-4H-pyran derivatives were synthesized via a multicomponent reaction involving acid, benzyloxy benzaldehyde, and malonitrile as tyrosinase inhibitors. Subsequently, the structures compounds characterized using FT-IR, 1 H-, 13 C-NMR spectroscopic analyses. The designed fall into three series: (1) 4-benzyloxy-phenyl kojopyran 6a – e , (2) 3-benzyloxy- phenyl 6f j (3) 4-benzyloxy-3-methoxy-phenyl derivative 6 k o . assessment inhibition activity was conducted L-Dopa substrate. Among compounds, 2-amino-4-(4-((4-fluorobenzyl)oxy)phenyl)-6-(hydroxymethyl)-8-oxo-4,8-dihydropyrano[3,2- b ]pyran-3-carbonitrile ( 6b ) demonstrated highest antityrosinase with competitive pattern (IC 50 = 7.69 ± 1.99 μM) compared to control agent 23.64 2.56 µM). Since compound racemic mixture, in silico studies performed for both R S enantiomers. - enantiomer showed critical interactions -enantiomer. Specifically, it established hydrogen bonds hydrophobic crucial highly conserved amino acids within enzyme's binding site target protein. Moreover, molecular dynamics simulations revealed that significant essential residues site, resulting stable complex throughout entire simulation run. drug-like ADMET properties predictions an acceptable profile Thus, can serve drug candidate develop more potent agents due its low toxicity high activity.

Language: Английский

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Synergistic Biomedical Potential and Molecular Docking Analyses of Coumarin–Triazole Hybrids as Tyrosinase Inhibitors: Design, Synthesis, In Vitro Profiling, and In Silico Studies

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(4), P. 532 - 532

Published: April 20, 2024

The tyrosinase enzyme has a vital role in the browning of vegetables and fruits biosynthesis melanin. In this work, we synthesized diverse library coumarin–triazole hybrids, these compounds were characterized by using suitable analytical techniques. Our research work extends beyond synthetic effort to explore therapeutic potential compounds. We put through meticulous vitro screening against enzyme, coumarin derivatives evinced good IC50 values range 0.339 ± 0.25 µM 14.06 0.92 µM. compounds, six found be more potent than standard ascorbic acid (IC50 = 11.5 1.00), among them, 17e 17f, being most active, exhibited remarkable anti-tyrosinase potential, with μM 3.148 0.23 μM, respectively. Furthermore, an silico modeling study was carried out determine key interactions protein (PDB ID: 2Y9X) thus authenticate our experimental findings. quantitative SAR studies correlation between their activity. docking verified results, ligand showed interaction core residues tyrosinase. This not only expands field hybrid synthesis but also provides valuable insights for development novel inhibitors.

Language: Английский

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