Changes in mitochondrial function and morphology contribute to the development of many neurological diseases. Parkinson's disease is one of the neurodegenerative diseases suspected to be associated with defects in mitochondrial function and quality control. The loss of dopaminergic neurons in the substantia nigra pars compacta is a well-known pathological feature of Parkinson's disease. It is important for elucidating the pathogenesis of Parkinson's disease to analyze mitochondrial function and morphology specific to dopaminergic neurons using live-cell imaging or electron microscopy. However, the cells differentiated into dopaminergic neurons from induced pluripotent stem cells generally comprise heterogeneous populations. We generated tyrosine hydroxylase (TH) reporter iPSC lines to distinguish dopaminergic neurons from other cells for live-cell imaging and electron microscopy. This review summarizes previous studies utilizing the TH reporter iPSC lines and discusses the importance of studying mitochondria specific to dopaminergic neurons. Additionally, it provides overviews of recent studies reporting changes in endoplasmic reticulum-mitochondrial contact sites in Parkinson's disease models.
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http://dx.doi.org/10.1007/s12565-024-00816-z | DOI Listing |
Front Cell Dev Biol
January 2025
The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
The main characteristics of Parkinson's disease (PD) are the loss of dopaminergic (DA) neurons and abnormal aggregation of cytosolic proteins. However, the exact pathogenesis of PD remains unclear, with ferroptosis emerging as one of the key factors driven by iron accumulation and lipid peroxidation. Glial cells, including microglia, astrocytes, and oligodendrocytes, serve as supportive cells in the central nervous system (CNS), but their abnormal activation can lead to DA neuron death and ferroptosis.
View Article and Find Full Text PDFGene networks encapsulate biological knowledge, often linked to polygenic diseases. While model system experiments generate many plausible gene networks, validating their role in human phenotypes requires evidence from human genetics. Rare variants provide the most straightforward path for such validation.
View Article and Find Full Text PDFIn the later stages of Parkinson's disease (PD), patients often manifest levodopa-induced dyskinesia (LID), compromising their quality of life. The pathophysiology underlying LID is poorly understood, and treatment options are limited. To move toward filling this treatment gap, the intrinsic and synaptic changes in striatal spiny projection neurons (SPNs) triggered by the sustained elevation of dopamine (DA) during dyskinesia were characterized using electrophysiological, pharmacological, molecular and behavioral approaches.
View Article and Find Full Text PDFZhejiang Da Xue Xue Bao Yi Xue Ban
January 2025
School of Medicine, Hangzhou City University, Zhejiang Provincial Key Laboratory of Novel Targets and Drug Study for Neural Repair, Hangzhou 310015, China.
Objectives: To investigate the protective effects and underlying mechanisms of extract on motor dysfunction in mouse model of Parkinson's disease (PD).
Methods: Eighty C57BL/6 male mice were randomly divided into five groups: control group, PD model group, levodopa treatment group (positive control group), low-dose GP treatment group (LD-GP group), and high-dose GP treatment group (HD-GP group), with 16 mice per group. The PD model was induced by injection of 6-hydroxydopamine into the substantia nigra pars reticulata in mice of last 5 groups.
J Hazard Mater
January 2025
Institute for Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China. Electronic address:
Microplastics are pervasive environmental contaminants found across diverse ecosystems, inducing toxic effects in a wide range of organisms. However, the neurotoxic effects of thermally degraded polystyrene (T-PS) and its underlying mechanisms remain poorly unexplored. In this study, Caenorhabditis elegans was exposed to environmentally relevant concentrations of T-PS (0.
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