Mitochondria are important organelles in virtually all eukaryotic cells, and are involved in a wide range of physiological and pathophysiological processes. Besides the generation of cellular energy in the form of adenosine triphosphate, mitochondria are also involved in calcium homeostasis, reactive oxygen species production and the activation of the intrinsic cell death pathway, thus determining cell survival and death. Mitochondrial abnormalities have been implicated in a wide range of disorders, including neurodegenerative disease such as Parkinson's disease (PD), and considered as a primary cause and central event responsible for the progressive loss of dopaminergic neurons in PD. Thus, reversion or attenuation of mitochondrial dysfunction should alleviate the severity or progression of the disease. The present review systematically summarizes the possible mechanisms associated with mitochondria‑mediated dopaminergic neuron damage in PD, in an attempt to elucidate the requirement for further studies for the development of effective PD treatments.
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http://dx.doi.org/10.3892/ijmm.2017.3255 | 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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