Hydroxytyrosol and dopamine metabolites: Anti-aggregative effect and neuroprotective activity against α-synuclein-induced toxicity

Gallardo-Fernández, Marta; Hornedo-Ortega, Ruth; Cerezo, Ana B.; Troncoso, Ana M.; García-Parrilla, M.C.

doi:10.1016/j.fct.2022.113542

Cited by 4 publications

(7 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[33][34][35] Concetta et al also found that curcumin and 3,4-dihydroxyphenylacetaldehyde (DOPAL) can also exert neuroprotective effects through the vitagenes system. 36,37 However, in the early stages of the disease, patients usually have no symptoms, but pathological changes have occurred in the nervous system.…”

Section: Discussionmentioning

confidence: 99%

Identification of key regulatory molecules in the early development stage of Alzheimer's disease

Huang,

Ou,

Zhang

2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, the incidence of which increases with age, and the pathological changes in the brain are irreversible. Recent studies have highlighted the essential role of long noncoding RNAs (lncRNAs) in AD by acting as competing endogenous RNAs (ceRNAs). Our aim was to construct lncRNA‐associated ceRNA regulatory networks composed of potential biomarkers for the early stage of AD. AD related datasets come from AlzData and GEO databases. The R package ‘Limma’ identifies differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases for functional enrichment analysis. Protein–protein interactions (PPIs) in DEGs were constructed in the STRING database, and Cytoscape software identified DEGs. Convergent functional genomics (CFG) analysis of differentially expressed hub genes (referred to as early‐DEGs) in the brain before the development of AD pathology. The AlzData database analyses the expression levels of early‐DEGs in different nerve cells. The lncRNA‐miRNA‐mRNA regulatory network was established according to the ceRNA hypothesis. We identified four lncRNAs (XIST, NEAT1, KCNQ1OT1 and HCG18) and four miRNAs (hsa‐let‐7c‐5p, hsa‐miR‐107, hsa‐miR‐129‐2‐3p and hsa‐miR‐214‐3p) were preliminarily identified as potential biomarkers for early AD, competitively regulating Atp6v0b, Atp6v1e1 Atp6v1f and Syt1. This study indicates that NEAT1, XIST, HCG18 and KCNQ1OT1 act as ceRNAs in competitive binding with miRNAs to regulate the expression of Atp6v0b, Atp6v1e1, Atp6v1f and Syt1 before the occurrence of pathological changes in AD.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of key regulatory molecules in the early development stage of Alzheimer's disease

Huang,

Ou,

Zhang

2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Moreover, a specific antibody was used to quantify the changes of α-synuclein affected by DOPAL, drawing a conclusion of the level of α-synuclein approximately in a range from 10 to 40 picogram per microgram of total proteins [ 37 ]. As for the connection between DOPAL and α-synuclein, to be specific, DOPAL inhibits the fibril formation of α-synuclein especially in the concentration of 20 μM and is in direct proportion to the aggregates of α-synuclein [ 38 ].…”

Section: Disruption Of Da Homeostasis In Parkinson's Diseasementioning

confidence: 99%

“…Additionally, it is reported that DOPAL plays a significant role in preventing α-synuclein aggregation, cytotoxicity and ROS production. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in innate immune cells is persistently activated by accumulated misfolded α-synuclein and releases proinflammatory cytokines to trigger the death of DA neurons [ 38 , 68 , 69 ]. Therefore, above results demonstrate connections of PD in varied aspects: endotoxic catecholamines, oxidative stress neuroinflammation, and antioxidant effectors [ 70 ].…”

Section: Role Of Synaptic Vesicular Proteins In Da Homeostasismentioning

confidence: 99%

“…As for the genetic perspective, a new compound heterozygous mutation (p. Leu1406Phefs*42 and p. Lys1321Glu) in SYNJ1 gene invalid AP2 binding sites causes neuronal dysfunction of synapses and vesicular endocytic recycling [ 124 ]. Phosphorylation of SYNJ1 at S1163 enhances the SYNJ1 D5-phosphatase activity, alters the interaction between SYNJ1 and endophilin, and promotes the efficient endocytosis of the active cycling vesicle pool at the expense of reserve pool vesicle endocytosis [ 37 , 38 ].…”

Section: Genetic Factors and Synaptic Vesicular Dysfunction In Pdmentioning

confidence: 99%

“…Inhibition of α-synuclein aggregation and destruction of aggregates are also major treatment strategies. In condition of co-incubating the α-synuclein and the metabolite of Hydroxytyrosol, 4-hydroxy-3-methoxyphenylethanol, the fluorescence signal was weakened and the formation of fiber was reduced by Thioflavin T fluorescence method, which both demonstrated the decreased concentration level of α-synuclein [ 38 ]. In addition, nanoparticle is one of the major research directions at present.…”

Section: Therapeutic Implications and Future Directionsmentioning

confidence: 99%

See 2 more Smart Citations

Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson’s Disease Pathogenesis

2023

Aging dis

View full text Add to dashboard Cite

Vestigial dopaminergic cells in PD have selectivity for a sub-class of hypersensitive neurons with the nigrostriatal dopamine (DA) tract. DA is modulated in pre-synaptic nerve terminals to remain stable. To be specific, proteins at DA release sites that have a function of synthesizing and packing DA in cytoplasm, modulating release and reingestion, and changing excitability of neurons, display regional discrepancies that uncover relevancy of the observed sensitivity to neurodegenerative changes. Although the reasons of a majority of PD cases are still indistinct, heredity and environment are known to us to make significant influences. For decades, genetic analysis of PD patients with heredity in family have promoted our comprehension of pathogenesis to a great extent, which reveals correlative mechanisms including oxidative stress, abnormal protein homeostasis and mitochondrial dysfunction. In this review, we review the constitution of presynaptic vesicle related to DA homeostasis and describe the genetic and environmental evidence of presynaptic dysfunction that increase risky possibility of PD concerning intracellular vesicle transmission and their functional outcomes. We summarize alterations in synaptic vesicular proteins with great involvement in the reasons of some DA neurons highly vulnerable to neurodegenerative changes. We generalize different potential targets and therapeutic strategies for different pathogenic mechanisms, providing a reference for further studies of PD treatment in the future. But it remains to be further researched on this recently discovered and converging mechanism of vesicular dynamics and PD, which will provide a more profound comprehension and put up with new therapeutic tactics for PD patients.

show abstract

Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort

Shebl,

El-Jaafary,

Saeed

et al. 2024

Front. Mol. Biosci.

View full text Add to dashboard Cite

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

show abstract

Hydroxytyrosol and dopamine metabolites: Anti-aggregative effect and neuroprotective activity against α-synuclein-induced toxicity

Cited by 4 publications

References 74 publications

Identification of key regulatory molecules in the early development stage of Alzheimer's disease

Identification of key regulatory molecules in the early development stage of Alzheimer's disease

Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson’s Disease Pathogenesis

Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort

Contact Info

Product

Resources

About