Perspective: Is a Closer Interaction between Experimental and Clinical Research Paradigms in Chronic Neurodegeneration, Such as Parkinson’s Disease, Necessary Again? DOI Creative Commons
Thomas Müller

Cells, Journal Year: 2022, Volume and Issue: 12(1), P. 157 - 157

Published: Dec. 30, 2022

This editorial discusses the current standstill in research Parkinson’s disease from a clinician’s point of view [...]

Language: Английский

Recent Advances in Characterization of Melanin Pigments in Biological Samples DOI Open Access
Kazumasa Wakamatsu, Shosuke Ito

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

Citations

23

Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort DOI Creative Commons
Nourhan Shebl, Shaimaa I El-Jaafary,

Ayman A. Saeed

et al.

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

Published: March 7, 2024

Introduction: Parkinson’s disease (PD) is the most common motor neurodegenerative worldwide. Given complexity of PD etiology and different metabolic derangements correlated to disease, metabolomics profiling patients a helpful tool identify patho-mechanistic pathways for development. Dopamine metabolism has been target several previous studies, which some have reported lower phenylalanine tyrosine levels in compared controls. Methods: In this study, we collected plasma from 27 patients, 18 reference controls, 8 high-risk controls perform metabolomic study using liquid chromatography-electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS). Results: Our findings revealed higher intensities trans-cinnamate, metabolite, Thus, hypothesize that shifted produce trans-cinnamate via L-phenylalanine ammonia lyase (PAL), instead producing tyrosine, dopamine precursor, hydroxylase (PAH). Discussion: these metabolites are precursors other pathways, many such as dopamine, norepinephrine, 3-hydroxyanthranilic acid, connects tryptophan, altered. Consequently, respect Metabolic Control Analysis (MCA) theory, tryptophan also Some tryptamine, melatonin, nicotinamide. assume alterations could contribute dopaminergic, adrenergic, serotonergic neurodegeneration happen disease.

Language: Английский

Citations

7

The Skin–Brain Axis: From UV and Pigmentation to Behaviour Modulation DOI Open Access
Anna A. Ascsillán, Lajos V. Kemény

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6199 - 6199

Published: June 4, 2024

The skin–brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson’s disease and many others. Recent evidence suggests that pathways regulating skin pigmentation may directly indirectly regulate behaviour. Conversely, CNS-driven neural hormonal responses have demonstrated pigmentation, e.g., under stress. Additionally, due the shared neuroectodermal origins of melanocytes neurons CNS, certain CNS diseases be linked pigmentation-related changes common regulators, MC1R variations. Furthermore, HPA analogue connects endocrine system, thereby allowing index possible abnormalities visibly. In this review, insight is provided into pigment production neuromelanin synthesis brain recent findings are summarised on how signalling skin, with particular focus interconnected central nervous system. Thus, review supply better understanding mechanism associations health disease.

Language: Английский

Citations

6

Riddles in the dark: Decoding the relationship between neuromelanin and neurodegeneration in locus coeruleus neurons DOI Creative Commons

Alexa F. Iannitelli,

David Weinshenker

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 152, P. 105287 - 105287

Published: June 15, 2023

Language: Английский

Citations

16

Artificial Intelligence-Assisted Optimization of Antipigmentation Tyrosinase Inhibitors: De Novo Molecular Generation Based on a Low Activity Lead Compound DOI
Hong Cai,

Wenchao Chen,

Jing Jiang

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(9), P. 7260 - 7275

Published: April 23, 2024

Artificial intelligence (AI) de novo molecular generation is a highly promising strategy in the drug discovery, with deep reinforcement learning (RL) models emerging as powerful tools. This study introduces fragment-by-fragment growth RL forward and optimization based on low activity lead compound. process integrates fragment growth-based reaction templates, while target docking drug-likeness prediction were simultaneously performed. comprehensive approach considers similarity, internal diversity, synthesizability, effectiveness, thereby enhancing quality efficiency of generation. Finally, series tyrosinase inhibitors generated synthesized. Most compounds exhibited more improved than lead, an optimal candidate compound surpassing effects kojic acid demonstrating significant antipigmentation zebrafish model. Furthermore, metabolic stability studies indicated susceptibility to hepatic metabolism. The proposed AI structural strategies will play role accelerating discovery improving traditional efficiency.

Language: Английский

Citations

5

Valorization of biomass polyphenols as potential tyrosinase inhibitors DOI
Thanh‐Nhat Pham, Elisabeth A. Cazier,

Emmanuelle Gormally

et al.

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 29(1), P. 103843 - 103843

Published: Nov. 23, 2023

Language: Английский

Citations

10

Diverse Functions of Parkin in Midbrain Dopaminergic Neurons DOI Creative Commons
Pingping Song, Dimitri Krainc

Movement Disorders, Journal Year: 2024, Volume and Issue: 39(8), P. 1282 - 1288

Published: June 10, 2024

Abstract Parkinson's disease (PD) is characterized by preferential degeneration of midbrain dopaminergic neurons that contributes to its typical clinical manifestation. Mutations in the parkin gene ( PARK2 ) represent a relatively common genetic cause early onset PD. Parkin has been implicated PINK1‐dependent mitochondrial quantity control targeting dysfunctional mitochondria lysosomes via mitophagy. Recent evidence suggests can be activated PINK1‐independent manner regulate synaptic function human neurons. Neuronal activity triggers CaMKII‐mediated activation and recruitment vesicles where promotes binding synaptojanin‐1 endophilin A1 facilitates vesicle endocytosis. In PD patient neurons, disruption this pathway on loss leads defective recycling accumulation toxic oxidized dopamine at least part explains vulnerability These findings suggest convergent mechanism for PD‐linked mutations parkin, synaptojanin‐1, highlight dysfunction as an pathogenic event © 2024 The Author(s). Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Language: Английский

Citations

3

Nuclear Alpha‐Synuclein in Parkinson’s Disease and the Malignant Transformation in Melanoma DOI Creative Commons
María E. Jiménez‐Capdeville,

Érika Chi-Ahumada,

Francisco García-Ortega

et al.

Neurology Research International, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Alpha‐synuclein (ASyn), a marker of Parkinson’s disease (PD) and other neurodegenerative processes, plays pivotal roles in neuronal nuclei synapses. ASyn its phosphorylated form at Serine 129 (p‐ASyn) are involved DNA protection repair, processes altered aging, neurodegeneration, cancer. Objective: To analyze the localization p‐ASyn skin biopsies PD patients melanoma. Methods: Biopsies from 26 patients, 20 melanoma 31 control subjects were probed analyzed with antibody by immunohistochemistry immunofluorescence. Nuclear positivity was quantified image analysis. Results: Peripheral nerve endings healthy show little immunopositivity but notable axonal presence PD. Control to along all epidermic strata scarce their cytoplasm. In contrast, nuclear is weaker, higher cytoplasmic intercellular presence. varied similar early stage rate empty intermediate total absence severe cases. Interpretation: These findings support cells that decreases almost disappears malignant transformation melanocytes, redistributing cytoplasm spaces. This confirms association between melanoma, providing crucial insights into role both diseases. Trial Registration: ClinicalTrials.gov identifier: NCT01380899 .

Language: Английский

Citations

0

Multidirectional research for the therapeutic potential of Phlomoides molucelloides (Bunge) Salmaki: LC-MS/MS, antioxidant, enzyme inhibition, and antiproliferative characteristics DOI

Anfal Izaldeen Mutar Al Kateeb,

Enis Fuat Tüfekci, Yasemin Çelik Altunoğlu

et al.

Process Biochemistry, Journal Year: 2024, Volume and Issue: 143, P. 302 - 314

Published: May 10, 2024

Language: Английский

Citations

2

Clarifying the association between Parkinson’s disease and vitiligo: a population-based large-scale study DOI Creative Commons
Khalaf Kridin,

Lior Ofir,

Orly Weinstein

et al.

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

Published: May 21, 2024

Our knowledge about the association between vitiligo and Parkinson's disease (PD) is sparse. We sought to investigate bidirectional epidemiological PD.

Language: Английский

Citations

2