DJ-1

We report highly enantioselective synthesis of L-α-hydroxy carboxylic acids (L-αHCAs) via enzymatic intramolecular Cannizzaro reaction of (hetero)aryl glyoxals in the presence of glutathione-independent human glyoxalase DJ-1. Combined with the optimized synthesis of D-αHCAs using glyoxalases I and II, this approach offers a general, scalable and operationally simple access to both enantiomers of α-hydroxy acids in moderate to excellent yields with uniformly high enantioselectivity.

BACKGROUND: Genetic underpinnings in Parkinson's disease (PD) and parkinsonian syndromes are challenging, and recent discoveries regarding their genetic pathways have led to potential gene-specific treatment trials. CASES: We report 3 X-linked levodopa (l-dopa)-responsive parkinsonism-epilepsy syndrome cases due to a hemizygous variant in the phosphoglycerate kinase 1 (PGK1) gene. The likely pathogenic variant NM_000291.4 (PGK1):c.950G > A;p.(Gly317Asp) was identified in a hemizygous state...

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the elderly for which there is no cure or disease-modifying therapy. Mitochondrial dysfunction and oxidative stress play a central role in dopaminergic neurodegeneration in PD. Therefore, antioxidants are considered a promising neuroprotective approach. In in vivo activity studies, 6-OHDA-induced oxidative stress in SH-SY5Y cells was established as a model of PD for cellular experiments. IIAVE (Ile-Ile-Ala-Val-Glu) was derived from Isochrysis zhanjiangensis octapeptide (IIAVEAGC), which has a small molecular weight...

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, the first being Alzheimer's disease. Patients with PD have a loss of dopaminergic neurons in the substantia nigra of the basal ganglia, which controls voluntary movements, causing a motor impairment as a result of dopaminergic signaling impairment. Studies have shown that mutations in several genes, such as SNCA, PARK2, PINK1, DJ-1, ATP13A2, and LRRK2, and the exposure to neurotoxic agents can potentially increase the chances of PD development...

Parkinson's disease (PD) is the most prevalent type of incurable movement disorder. Recent research findings propose that the familial PD-associated molecule DJ-1 exists in cerebrospinal fluid (CSF) and that its levels may be altered as Parkinson's disease advances. By using a molecularly imprinted polymer (MIP) as an artificial receptor, it becomes possible to create a functional MIP with predetermined selectivity for various templates, particularly for the DJ-1 biomarker associated with Parkinson's disease...

OBJECTIVE: DJ-1 is an oncoprotein secreted by cancer cells. However, the physiological and pathological significance of DJ-1 secretion is not clearly understood. This study investigated the clinical value of serum DJ-1 in lung adenocarcinoma (LUAD). METHODS: The study involved 224 LUAD patients, 110 patients with benign pulmonary disease and 100 healthy controls from the First Affiliated Hospital of Nanjing Medical University. We detected the expression of DJ-1 in lung cell lines in vitro ...

Previous clinical reports have shown that capecitabine, an oral prodrug of 5-fluorouracil (5-Fu), can induce peripheral neuropathy, resulting in numbness, paresthesia and hypoesthesia. However, the mechanism through which capecitabine causes peripheral nerve injury remains unclear. Here, we demonstrate that systemic administration of capecitabine leads to myelin abnormalities in the peripheral nerves of mice, which are possibly attributed to the death of Schwann cells, the myelinating cells in the peripheral nervous system...

Coronary artery ectasia (CAE) is defined as abnormal dilation of a coronary artery with a diameter exceeding that of adjacent normal arterial segment by >1.5 times. CAE is a pathological entity of the coronary arteries and characterized as a variant of coronary atherosclerosis. CAE frequently coexists with coronary artery disease (CAD). While inflammation appears to be involved, the pathophysiology of CAE remains unclear. Damage-associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue, are deemed as alarm signals by the innate immune system...

Parkinson's disease (PD) is the second most prevalent neurodegenerative movement disorder worldwide, which is primarily characterized by motor impairments. Even though multiple hypotheses have been proposed over the decades that explain the pathogenesis of PD, presently, there are no cures or promising preventive therapies for PD. This could be attributed to the intricate pathophysiology of PD and the poorly understood molecular mechanism. To address these challenges comprehensively, a thorough disease model is imperative for a nuanced understanding of PD's underlying pathogenic mechanisms...

Cyanamides have emerged as privileged scaffolds in covalent inhibitors of deubiquitinating enzymes (DUBs). However, many compounds with a cyanopyrrolidine warhead show cross-reactivity toward small subsets of DUBs or toward the protein deglycase PARK7/DJ-1, hampering their use for the selective perturbation of a single DUB in living cells. Here, we disclose N'-alkyl,N-cyanopiperazines as structures for covalent enzyme inhibition with exceptional specificity for the DUB UCHL1 among 55 human deubiquitinases and with potent target engagement in cells...

[This retracts the article DOI: 10.1155/2022/9912776.].

BACKGROUND: Melanoma, the most lethal skin cancer type, occurs more frequently in Parkinson's disease (PD), and PD is more frequent in melanoma patients, suggesting disease mechanisms overlap. α-synuclein, a protein that accumulates in PD brain, and the oncogene DJ-1, which is associated with PD autosomal recessive forms, are both elevated in melanoma cells. Whether this indicates melanoma progression or constitutes a protective response remains unclear. We hereby investigated the molecular mechanisms through which α-synuclein and DJ-1 interact, suggesting novel biomarkers and targets in melanoma...

INTRODUCTION: Advances in sequencing technologies have enabled extensive genetic testing on an individual basis. Genome-wide association studies (GWAS) have provided insight into the pathophysiology of PD. Additionally, direct-to-consumer genetic testing has enabled the identification of genetic diseases and risk factors without genetic counselling. As genetics increasingly permeates clinical practice, this paper aims to summarise the most important information on genetics in PD forclinical practitioners...

Several studies have reported the effects of DJ-1 gene and miR-199a/b-3p on HCC development. However, whether miR-199a/b-3p regulates HCC progression through a novel compensatory signaling pathway involving DJ-1, Ras, and PI3K/AKT remains unknown. We used (TCGA, HPA, miRWalk and Target scan) databases, cancer and para-tissue HCC patients, dual-luciferase reporter gene analysis, proteomic imprinting, qPCR, cell proliferation, scratch, transport, and flow cytometry to detect the molecular mechanism of DJ-1 and miR-199a/b-3p co-expression in HCC cell lines...

ETHNOPHARMACOLOGICAL RELEVANCE: SuanZaoRen Decoction (SZRD), a famous herbal prescription, and has been widely proven to have positive therapeutic effects on insomnia, depression and Alzheimer's disease (AD). However, the anti-AD molecular mechanism of SZRD remains to be further investigated. AIM OF THE STUDY: To elucidate the molecular mechanism of SZRD's improvement in AD's neuronal loss, synaptic damage and ferroptosis by regulating DJ-1/Nrf2 signaling pathway...

DJ-1 is significantly elevated in various malignancies. However, the clinical significance of DJ-1 in hormone receptor (HR)-positive (HR+) breast cancer remains unclear. We evaluated DJ-1 expression in different databases and validated in vitro assay by RT-PCR and western blot among HR+ breast cancer. The correlations between DJ-1 level and tumor-immune were calculated. Mutational landscape, enriched signaling pathways, and drug sensitivity analyses were also assessed between DJ-1 high and low-expression groups...

BACKGROUND: Keloids are aberrant dermal wound healing characterized by invasive growth, extracellular matrix deposition, cytokine overexpression and easy recurrence. Many factors have been implicated as pathological causes of keloids, particularly hyperactive inflammation, tension alignment and genetic predisposition. S-Nitrosylation (SNO), a unique form of protein modification, is associated with the local inflammatory response but its function in excessive fibrosis and keloid formation remains unknown...

Mitochondrial dysregulation, such as mitochondrial complex I deficiency, increased oxidative stress, perturbation of mitochondrial dynamics and mitophagy, has long been implicated in the pathogenesis of PD. Initiating from the observation that mitochondrial toxins cause PD-like symptoms and mitochondrial DNA mutations are associated with increased risk of PD, many mutated genes linked to familial forms of PD, including PRKN , PINK1 , DJ-1 and SNCA , have also been found to affect the mitochondrial features...

INTRODUCTION: There has been a bias in the existing literature on Parkinson's disease (PD) genetics as most studies involved patients of European ancestry, mostly in Europe and North America. Our target was to review published research data on the genetic profile of PD patients of non-European or mixed ancestry. METHODS: We reviewed articles published during the 2000-2023 period, focusing on the genetic status of PD patients of non-European origin (Indian, East and Central Asian, Latin American, sub-Saharan African and Pacific islands)...

Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substania nigra (SN) and is associated with progressive motor impairment. PD is classified into familial and sporadic forms. The first genetic association studies in PD reported the involvement of Synuclein alpha (SNCA) mutations in the pathobiology of familial PD. Subsequent studies suggested mutations in PTEN-induced putative kinase 1 (PINK1), PARKIN, leucine repeat kinase-2 (LRRK2), and DJ-1 causing familial PD...