Products of the Parkinson’s-disease related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival

Toyoda, Yusuke; Erkut, Cihan; Pan‐Montojo, Francisco; Boland, Sebastian; Stewart, Martin P.; ller, Daniel J. M; Wurst, Wolfgang; Hyman, Anthony; Kurzchalia, Teymuras V.

doi:10.1101/006916

Cited by 7 publications

(9 citation statements)

References 55 publications

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“…bulgaricus over conventional probiotic bacteria based on the stereoisomer of lactic acid produced was discovered. Toyoda et al [11] showed that the survival of cultured neurons defective in Parkinson's disease is enhanced by D-lactate. Since D-lactate is produced by Lb.…”

Section: Introductionmentioning

confidence: 99%

Microbial diversity and health-promoting properties of the traditional Bulgarian yogurt

Velikova

Petrov

Lozanov

et al. 2018

Biotechnology & Biotechnological Equipment

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Bulgarian yogurt is usually associated with good health and longevity. This study aimed to analyse the current microbial content of homemade Bulgarian yogurt. Identification by 16S rDNA sequencing revealed that out of 76 isolated strains, 53% belonged to Lactobacillus delbrueckii subsp. bulgaricus, 14% to other lactobacilli, and 32% to lactic acid cocci (Streptococcus thermophilus, Pediococcus acidilactici, Enterococcus faecium and Leuconostoc). All isolates inhibited the growth of pathogenic bacteria (10% of them by the putative action of bacteriocins); 18 isolates were able to produce extracellular exopolysaccharides (EPS), whereas 24% of them demonstrated extremely high proteolytic activity. Remarkably, 10 Lb. bulgaricus strains produced prebiotic galactooligosaccharides (GOS). High-resolution accurate mass spectrometry (HRAMS) analysis revealed production of tri-and tetrasaccharides containing atypical b(1!4) glycosidic bonds, reported for the first time for Lb. bulgaricus. Based on the beneficial features, along with good technological behaviour, we recommend several isolates as highly promising for Bulgarian yogurt starters.

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Section: Introductionmentioning

confidence: 99%

Microbial diversity and health-promoting properties of the traditional Bulgarian yogurt

Velikova

Petrov

Lozanov

et al. 2018

Biotechnology & Biotechnological Equipment

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“…All animal procedures were performed according to the German Law for Animal Experiments (Tierversuchsgesetzt) and were approved by the Regierung von Oberbayern (The government from Bayern, Germany). Primary mesencephalic neuronal cell cultures were prepared as previously described [ 41 ]. Briefly, E14.5 embryos were obtained from C57JBL6 pregnant mice after cervical dislocation.…”

Section: Methodsmentioning

confidence: 99%

A study on the modulation of alpha-synuclein fibrillation by Scutellaria pinnatifida extracts and its neuroprotective properties

et al. 2017

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Aggregation of alpha-synuclein (α-SN) is a key pathogenic event in Parkinson’s disease (PD) leading to dopaminergic degeneration. The identification of natural compounds inhibiting α-SN aggregation may have a major role in treating PD. Different Scutellaria species are known as valuable medicinal plants, primarily due to their high flavonoid levels. Scutellaria pinnatifida (S. pinnatifida) is endemic to Iran; however, the knowledge of its pharmaceutical properties is limited. Here we report that S. pinnatifida extracts have an anti-fibrillation effect on α-SN aggregation and neuroprotective properties on PC12 and primary dopaminergic neurons. Treatment during α-SN fibril formation with S. pinnatifida extracts showed that the extractions performed with dichloromethane (DCMEx) and n-butanol (BuOHEx) strongly inhibited α-SN fibrillation. TLC-based analysis revealed that S. pinnatifida contains a great amount of flavonoids with high antioxidant properties as shown using a radical scavenging assay. Further analysis using HPLC and Mass spectroscopy on the DCMEx revealed the presence of baicalein in this extract. We then selected the more efficient extracts based on cell viability and ROS scavenging on PC12 cells and tested their neuroprotective properties on primary dopaminergic neurons. Our results showed the extracts strongly protected against α-SN oligomers. Surprisingly, they also neutralized the severe toxicity of paraquat. Therefore, S. pinnatifida may be a potential valuable medicinal herb for further studies related to the treatment of PD.

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“…However, as most of these mutations lead to a loss of function, gene therapy has been suggested for PARK2 and GBA . The potential use of the DJ‐1 products glycolate and D‐lactate, which are neuroprotective, has been explored as well . In the case of MSA, mutations in the coenzyme Q10‐encoding gene COQ2 have been associated with an increased risk of suffering this disease; however, treatment with coenzyme Q10 did not slow down the progression of PD in a phase III study, suggesting that its efficacy may be limited by other factors.…”

Section: Therapeutic Alternatives For Synucleinopathiesmentioning

confidence: 99%

Combination therapies: The next logical Step for the treatment of synucleinopathies?

Valera

Masliah

2015

Movement Disorders

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Currently there are no disease-modifying alternatives for the treatment of most neurodegenerative disorders. The available therapies for diseases such as Parkinson’s disease (PD), PD dementia (PDD), Dementia with Lewy bodies (DLB) and Multiple system atrophy (MSA), in which the protein alpha-synuclein (α-syn) accumulates within neurons and glial cells with toxic consequences, are focused on managing the disease symptoms. However, utilizing strategic drug combinations and/or multi-target drugs might increase the treatment efficiency when compared to monotherapies. Synucleinopathies are complex disorders that progress through several stages, and toxic α-syn aggregates exhibit prion-like behavior spreading from cell to cell. Therefore, it follows that these neurodegenerative disorders might require equally complex therapeutic approaches in order to obtain significant and long-lasting results. Hypothetically, therapies aimed at reducing α-syn accumulation and cell-to-cell transfer, such as immunotherapy against α-syn, could be combined with agents that reduce neuroinflammation with potential synergistic outcomes. Here we review the current evidence supporting this type of approach, suggesting that such rational therapy combinations, together with the use of multi-target drugs, may hold promise as the next logical step for the treatment of synucleinopathies.

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Products of the Parkinson’s-disease related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival

Abstract: peer-reviewed)

Cited by 7 publications

References 55 publications

Microbial diversity and health-promoting properties of the traditional Bulgarian yogurt

Microbial diversity and health-promoting properties of the traditional Bulgarian yogurt

A study on the modulation of alpha-synuclein fibrillation by Scutellaria pinnatifida extracts and its neuroprotective properties

Combination therapies: The next logical Step for the treatment of synucleinopathies?

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