DJ-1 in Parkinson’s Disease: Clinical Insights and Therapeutic Perspectives

Repici, Mariaelena; Giorgini, Flaviano

doi:10.3390/jcm8091377

Cited by 122 publications

(93 citation statements)

References 88 publications

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“…One of the examples is the oxidative modification of the DJ-1 protein. The DJ-1 protein, which contains 189 amino acids, has been linked to PD because the loss of its functions causes disease with parkinsonian characteristics [55]. The oxidative modifications in a single amino acid of the DJ-1 protein are sufficient to favor PD development.…”

Section: Processed Meat Containing Oxidized Proteins Inmentioning

confidence: 99%

Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson’s Disease

Miranda-Díaz

García-Sánchez

Cardona-Muñoz

2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress plays a fundamental role in the pathogenesis of Parkinson’s disease (PD). Oxidative stress appears to be responsible for the gradual dysfunction that manifests via numerous cellular pathways throughout PD progression. This review will describe the prooxidant effect of excessive consumption of processed food. Processed meat can affect health due to its high sodium content, advanced lipid oxidation end-products, cholesterol, and free fatty acids. During cooking, lipids can react with proteins to form advanced end-products of lipid oxidation. Excessive consumption of different types of carbohydrates is a risk factor for PD. The antioxidant effects of some foods in the regular diet provide an inconclusive interpretation of the environment’s mechanisms with the modulation of oxidation stress-induced PD. Some antioxidant molecules are known whose primary mechanism is the neuroprotective effect. The melatonin mechanism consists of neutralizing reactive oxygen species (ROS) and inducing antioxidant enzyme’s expression and activity. N-acetylcysteine protects against the development of PD by restoring levels of brain glutathione. The balanced administration of vitamin B3, ascorbic acid, vitamin D and the intake of caffeine every day seem beneficial for brain health in PD. Excessive chocolate intake could have adverse effects in PD patients. The findings reported to date do not provide clear benefits for a possible efficient therapeutic intervention by consuming the nutrients that are consumed regularly.

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Section: Processed Meat Containing Oxidized Proteins Inmentioning

confidence: 99%

Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson’s Disease

Miranda-Díaz

García-Sánchez

Cardona-Muñoz

2020

Oxidative Medicine and Cellular Longevity

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“…Concerning VEGF, and it was already mentioned, this factor plays an important role in the neurorescuing of DAn, by interacting with different players in the potentiation of the dopaminergic system [52,54]. Similarly, it is DJ-1 that has been described as a major player and target for PD modeling and repair [2,55,56]. Notably, studies have demonstrated that DJ-1 deficiency sensitizes microglial cells to release pro-inflammatory cytokines (e.g.…”

Section: Discussionmentioning

confidence: 98%

Preclinical Comparison of Stem Cells Secretome and Levodopa Application in a 6-Hydroxydopamine Rat Model of Parkinson’s Disease

Teixeira

Vilaça-Faria

Domingues

et al. 2020

Cells

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Parkinson’s Disease (PD) is characterized by the massive loss of dopaminergic neurons, leading to the appearance of several motor impairments. Current pharmacological treatments, such as the use of levodopa, are yet unable to cure the disease. Therefore, there is a need for novel strategies, particularly those that can combine in an integrated manner neuroprotection and neuroregeneration properties. In vitro and in vivo models have recently revealed that the secretome of mesenchymal stem cells (MSCs) holds a promising potential for treating PD, given its effects on neural survival, proliferation, differentiation. In the present study, we aimed to access the impact of human bone marrow MSCs (hBM-MSCs) secretome in 6-hydroxydopamine (6-OHDA) PD model when compared to levodopa administration, by addressing animals’ motor performance, and substantia nigra (SN), and striatum (STR) histological parameters by tyrosine hydroxylase (TH) expression. Results revealed that hBM-MSCs secretome per se appears to be a modulator of the dopaminergic system, enhancing TH-positive cells expression (e.g., dopaminergic neurons) and terminals both in the SN and STR when compared to the untreated group 6-OHDA. Such finding was positively correlated with a significant amelioration of the motor outcomes of 6-OHDA PD animals (assessed by the staircase test). Thus, the present findings support hBM-MSCs secretome administration as a potential therapeutic tool in treating PD, and although we suggest candidate molecules (Trx1, SEMA7A, UCHL1, PEDF, BDNF, Clusterin, SDF-1, CypA, CypB, Cys C, VEGF, DJ-1, Gal-1, GDNF, CDH2, IL-6, HSP27, PRDX1, UBE3A, MMP-2, and GDN) and possible mechanisms of hBM-MSCs secretome-mediated effects, further detailed studies are needed to carefully and clearly define which players may be responsible for its therapeutic actions. By doing so, it will be reasonable to presume that potential treatments that can, per se, or in combination modulate or slow PD may lead to a rational design of new therapeutic or adjuvant strategies for its functional modeling and repair.

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“…Mechanistically, this promising HDAC inhibitor can up-regulate the protein deglycase (DJ-1). DJ-1 acts as a versatile prosurvival factor in DA activating different protective mechanisms such as regulation of mitochondria, antioxidative stress response, and up-regulating total intracellular glutathione in response to a diverse range of PD related insults (Repici and Giorgini, 2019 ).…”

Section: Neuroinflammation In Parkinson’s Diseasementioning

confidence: 99%

Glia Crosstalk in Neuroinflammatory Diseases

Bernaus

Blanco

Sevilla

2020

Front. Cell. Neurosci.

106

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Neuroinflammation constitutes a fundamental cellular process to signal the loss of brain homeostasis. Glial cells play a central role in orchestrating these neuroinflammation processes in both deleterious and beneficial ways. These cellular responses depend on their intercellular interactions with neurons, astrocytes, the blood–brain barrier (BBB), and infiltrated T cells in the central nervous system (CNS). However, this intercellular crosstalk seems to be activated by specific stimuli for each different neurological scenario. This review summarizes key studies linking neuroinflammation with certain neurodegenerative diseases such as Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) and for the development of better therapeutic strategies based on immunomodulation.

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DJ-1 in Parkinson’s Disease: Clinical Insights and Therapeutic Perspectives

Cited by 122 publications

References 88 publications

Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson’s Disease

Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson’s Disease

Preclinical Comparison of Stem Cells Secretome and Levodopa Application in a 6-Hydroxydopamine Rat Model of Parkinson’s Disease

Glia Crosstalk in Neuroinflammatory Diseases

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