Reactive oxygen species (ROS) elicited by oxidative stress are widely recognized as a major initiator in the dege-neration of dopaminergic neurons distinctive of Parkinson's disease (PD). The interaction of ROS with mitochondria triggers sequential events in the mitochondrial cell death pathway, which is thought to be responsible for ROS-mediated neurodegeneration in PD. α-lipoic acid (LA) is a pleiotropic compound with potential pharmacotherapeutic value against a range of pathophysiological insults. Its protective actions against oxidative damage by scavenging ROS and reducing production of free radicals have been reported in various in vitro and in vivo systems. This study analyzed the ability of LA to protect PC12 neuronal cells from toxicity of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which is known to kill dopaminergic neurons selectively and to cause severe parkinsonism-like symptoms in humans and primate animals. Our results demonstrate that the apoptosis of PC12 cells elicited by MPP+ could be significantly prevented by pretreatment with LA for 1 h. In addition, LA inhibits intercellular ROS levels and the mitochondrial transmembrane permeability, the key players in the pathogenesis of PD, thereby protecting dopaminergic neuronal cells against oxidative damage.
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http://dx.doi.org/10.3892/ijmm.2013.1361 | DOI Listing |
Am J Physiol Cell Physiol
January 2025
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro.
O-GlcNAcylation is a post-translational modification characterized by the covalent attachment of a single moiety of GlcNAc on serine/threonine residues in proteins. Tyrosine hydroxylase (TH), the rate-limiting step enzyme in the catecholamine synthesis pathway and responsible for production of the dopamine precursor, L-DOPA, has its activity regulated by phosphorylation. Here, we show an inverse feedback mechanism between O-GlcNAcylation and phosphorylation of TH at serine 40 (TH pSer40).
View Article and Find Full Text PDFBackground: Deficiency in the lysosomal enzyme, glucocerebrosidase (GCase), caused by mutations in the GBA1 gene, is the most common genetic risk factor for Parkinson's disease (PD). However, the consequence of reduced enzyme activity within neural cell sub-types remains ambiguous. Thus, the purpose of this study was to define the effect of GCase deficiency specifically in human astrocytes and test their non-cell autonomous influence upon dopaminergic neurons in a midbrain organoid model of PD.
View Article and Find Full Text PDFFew of the many chemicals that regulatory agencies are charged with assessing for risk have been carefully tested for developmental neurotoxicity (DNT). To speed up testing efforts, as well as to reduce the use of vertebrate animals, great effort is being devoted to alternate laboratory models for testing DNT. A major mechanism of DNT is altered neuronal architecture resulting from chemical exposure during neurodevelopment.
View Article and Find Full Text PDFPeerJ
January 2025
Medical section, Jiang Ling County People's Hospital, Hubei, Jiangling County, Jingzhou City, China.
Background: This study investigates the protective properties of melatonin in an Parkinson's disease (PD) model, focusing on the underlying mechanisms involving heat shock proteins (HSPs).
Methods: Twelve adult male C57BL/6 mice were randomly divided into four groups (normal control, melatonin control, Parkinson's model, and melatonin treatment; = 3 per group) and housed in a single cage. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected intraperitoneally in the Parkinson's model and treatment groups to establish a subacute PD model, while controls received saline.
Mol Psychiatry
January 2025
Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli, 80078, Naples, Italy.
Lysosomal storage disorders characterized by defective heparan sulfate (HS) degradation, such as Mucopolysaccharidosis type IIIA-D (MPS-IIIA-D), result in neurodegeneration and dementia in children. However, dementia is preceded by severe autistic-like behaviours (ALBs), presenting as hyperactivity, stereotypies, social interaction deficits, and sleep disturbances. The absence of experimental studies on ALBs' mechanisms in MPS-III has led clinicians to adopt symptomatic treatments, such as antipsychotics, which are used for non-genetic neuropsychiatric disorders.
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