Neurochemical effects of the R form of α-lipoic acid and its neuroprotective mechanism in cellular models of Parkinson’s disease

2017 ◽  
Vol 87 ◽  
pp. 86-94 ◽  
Author(s):  
Hong Zhao ◽  
Xingcheng Zhao ◽  
Lijuan Liu ◽  
Hongxu Zhang ◽  
Mingwen Xuan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lipoic Acid ◽  
Cellular Models

The Contributions Of Antioxidant Activity Of Lipoic Acid In Reducing Neurogenerative Progression Of Parkinson’s Disease: A Review

2010 ◽  
Vol 121 (2) ◽  
pp. 51-57 ◽  
Author(s):  
Dayane Pessoa De Araújo ◽  
Rodrigo De Freitas Guimarães Lobato ◽  
José Rodolfo Lopes De Paiva Cavalcanti ◽  
Luis Rafael Leite Sampaio ◽  
Paulo Victor Pontes Araújo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Antioxidant Activity ◽  
Parkinson's Disease ◽  
Lipoic Acid

scholarly journals Alteration in the Cerebrospinal Fluid Lipidome in Parkinson’s Disease: A Post-Mortem Pilot Study

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 491
Author(s):  
Joaquín Fernández-Irigoyen ◽  
Paz Cartas-Cejudo ◽  
Marta Iruarrizaga-Lejarreta ◽  
Enrique Santamaría
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Ultra Performance Liquid Chromatography ◽  
Small Population ◽  
Control Group ◽  
Post Mortem ◽  
Cellular Models ◽  
Flight Mass Spectrometry ◽  
Lipid Species

Lipid metabolism is clearly associated to Parkinson’s disease (PD). Although lipid homeostasis has been widely studied in multiple animal and cellular models, as well as in blood derived from PD individuals, the cerebrospinal fluid (CSF) lipidomic profile in PD remains largely unexplored. In this study, we characterized the post-mortem CSF lipidomic imbalance between neurologically intact controls (n = 10) and PD subjects (n = 20). The combination of dual extraction with ultra-performance liquid chromatography-electrospray ionization quadrupole-time-of-flight mass spectrometry (UPLC-ESI-qToF-MS/MS) allowed for the monitoring of 257 lipid species across all samples. Complementary multivariate and univariate data analysis identified that glycerolipids (mono-, di-, and triacylglycerides), saturated and mono/polyunsaturated fatty acids, primary fatty amides, glycerophospholipids (phosphatidylcholines, phosphatidylethanolamines), sphingolipids (ceramides, sphingomyelins), N-acylethanolamines and sterol lipids (cholesteryl esters, steroids) were significantly increased in the CSF of PD compared to the control group. Interestingly, CSF lipid dyshomeostasis differed depending on neuropathological staging and disease duration. These results, despite the limitation of being obtained in a small population, suggest extensive CSF lipid remodeling in PD, shedding new light on the deployment of CSF lipidomics as a promising tool to identify potential lipid markers as well as discriminatory lipid species between PD and other atypical parkinsonisms.

scholarly journals The activities of LRRK2 and GCase are positively correlated in clinical biospecimens and experimental models of Parkinson’s disease

2021 ◽  
Author(s):  
Maria Kedariti ◽  
Emanuele Frattini ◽  
Pascale Baden ◽  
Susanna Cogo ◽  
Laura Civiero ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Kinase Activity ◽  
Experimental Models ◽  
Cellular Functions ◽  
Gene Encoding ◽  
Cellular Models ◽  
Lrrk2 Kinase ◽  
The Impact ◽  
Lrrk2 Kinase Activity

AbstractLRRK2 is a kinase involved in different cellular functions, including autophagy, endolysosomal pathways and vesicle trafficking. Mutations in LRRK2 cause autosomal dominant forms of Parkinson’s disease (PD). Heterozygous mutations in GBA1, the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), are the most common genetic risk factors for PD. Moreover, GCase function is altered in idiopathic PD and in other genetic forms of the disease. Recent work suggests that LRRK2 kinase activity can regulate GCase function. However, both a positive and a negative correlation have been described. To gain insights into the impact of LRRK2 on GCase, we investigated GCase levels and activity in LRRK2 G2019S knockin mice, in clinical biospecimens from PD patients carrying this mutation and in patient-derived cellular models. In these models we found a positive correlation between the activities of LRRK2 and GCase, which was further confirmed in cell lines with genetic and pharmacological manipulation of LRRK2 kinase activity. Overall, our study indicates that LRRK2 kinase activity affects both the levels and the catalytic activity of GCase.

Neuroprotective effect of the carnosine – α-lipoic acid nanomicellar complex in a model of early-stage Parkinson's disease

2018 ◽  
Vol 95 ◽  
pp. 254-259 ◽  
Author(s):  
Olga I. Kulikova ◽  
Daniil S. Berezhnoy ◽  
Sergey L. Stvolinsky ◽  
Alexander V. Lopachev ◽  
Valentina S. Orlova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lipoic Acid ◽  
Early Stage ◽  
Neuroprotective Effect

scholarly journals STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson’s disease

2015 ◽  
Vol 112 (4) ◽  
pp. 1202-1207 ◽  
Author(s):  
Pradeep K. Kurup ◽  
Jian Xu ◽  
Rita Alexandra Videira ◽  
Chimezie Ononenyi ◽  
Graça Baltazar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Tyrosine Phosphatase ◽  
Dopaminergic Neurons ◽  
Tyrosine Phosphatase ◽  
E3 Ligase ◽  
Substantia Nigra Pars Compacta ◽  
Rat Striatum ◽  
Protein Tyrosine ◽  
Cellular Models

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). The loss of SNc dopaminergic neurons affects the plasticity of striatal neurons and leads to significant motor and cognitive disabilities during the progression of the disease. PARK2 encodes for the E3 ubiquitin ligase parkin and is implicated in genetic and sporadic PD. Mutations in PARK2 are a major contributing factor in the early onset of autosomal-recessive juvenile parkinsonism (AR-JP), although the mechanisms by which a disruption in parkin function contributes to the pathophysiology of PD remain unclear. Here we demonstrate that parkin is an E3 ligase for STEP61 (striatal-enriched protein tyrosine phosphatase), a protein tyrosine phosphatase implicated in several neuropsychiatric disorders. In cellular models, parkin ubiquitinates STEP61 and thereby regulates its level through the proteasome system, whereas clinically relevant parkin mutants fail to do so. STEP61 protein levels are elevated on acute down-regulation of parkin or in PARK2 KO rat striatum. Relevant to PD, STEP61 accumulates in the striatum of human sporadic PD and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice. The increase in STEP61 is associated with a decrease in the phosphorylation of its substrate ERK1/2 and the downstream target of ERK1/2, pCREB [phospho-CREB (cAMP response element-binding protein)]. These results indicate that STEP61 is a novel substrate of parkin, although further studies are necessary to determine whether elevated STEP61 levels directly contribute to the pathophysiology of PD.

scholarly journals Reduced synaptic activity and dysregulated extracellular matrix pathways are common phenotypes in midbrain neurons derived from sporadic and mutation-associated Parkinson's disease patients

2022 ◽  
Author(s):  
Shani Stern ◽  
Shong Lau ◽  
Andreea Manole ◽  
Idan Rosh ◽  
Menahem Percia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Extracellular Matrix ◽  
Parkinson's Disease ◽  
Synaptic Activity ◽  
Cellular Models ◽  
Midbrain Neurons ◽  
Severe Reduction ◽  
Show Evidence ◽  
Induced Pluripotent ◽  
The Relationship

Several mutations that cause Parkinson's disease (PD) have been identified over the past decade. These account for 15-25% of PD cases; the rest of the cases are considered sporadic. Currently, it is accepted that PD is not a single monolithic disease but rather a constellation of diseases with some common phenotypes. While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: Neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as the SNCA and LRRK2 and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, shows pathways and mechanisms that are central and convergent to PD and suggests a strong involvement of the tetra-partite synapse in PD pathology.

scholarly journals Interaction Among Mitochondria, Mitogen-Activated Protein Kinases, and Nuclear Factor-κB in Cellular Models of Parkinson's Disease

2002 ◽  
Vol 74 (4) ◽  
pp. 1384-1392 ◽  
Author(s):  
David S. Cassarino ◽  
Erik M. Halvorsen ◽  
Russell H. Swerdlow ◽  
Nicole N. Abramova ◽  
W. Davis Parker ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Kinases ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Mitogen Activated Protein Kinases ◽  
Cellular Models ◽  
Mitogen Activated Protein

Pre-treatment with R-Lipoic Acid Alleviates the Effects of GSH Depletion in PC12 Cells: Implications for Parkinson’s Disease Therapy

2002 ◽  
Vol 23 (4-5) ◽  
pp. 479-486 ◽  
Author(s):  
S. Bharath ◽  
B.C. Cochran ◽  
M. Hsu ◽  
J. Liu ◽  
B.N. Ames ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Lipoic Acid ◽  
Disease Therapy ◽  
Pre Treatment
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