Effects of Calcium Ion Dyshomeostasis and Calcium Ion-Induced Excitotoxicity in Parkinson’s Disease
Calcium ions (Ca<sup>2+</sup>) are vital intracellular messengers that regulate a multitude of neuronal functions, including synaptic transmission, plasticity, exocytosis, and cell survival. Neuronal cell death can occur through a variety of mechanisms, including excitotoxicity, apoptosi...
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2024-12-01
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| author | Daleum Nam Hyejung Kim Sun Jung Han Ilhong Son Dong Hwan Ho |
| author_facet | Daleum Nam Hyejung Kim Sun Jung Han Ilhong Son Dong Hwan Ho |
| author_sort | Daleum Nam |
| collection | DOAJ |
| description | Calcium ions (Ca<sup>2+</sup>) are vital intracellular messengers that regulate a multitude of neuronal functions, including synaptic transmission, plasticity, exocytosis, and cell survival. Neuronal cell death can occur through a variety of mechanisms, including excitotoxicity, apoptosis, and autophagy. In the context of excitotoxicity, the excessive release of glutamate in the synapses can trigger the activation of postsynaptic receptors. Upon activation, Ca<sup>2+</sup> influx into the cell from the extracellular space via their associated ion channels, most notably L-type Ca<sup>2+</sup> channels. Previous studies have indicated that α-synuclein (α-syn), a typical cytosolic protein, plays a significant role in the pathogenesis of Parkinson’s disease (PD). It is also worth noting that the aggregated form of α-syn has the capacity to affect Ca<sup>2+</sup> homeostasis by altering the function of Ca<sup>2+</sup> regulation. The upregulation of leucine-rich repeat kinase 2 (LRRK2) is closely associated with PD pathogenesis. LRRK2 mutants exhibit a dysregulation of calcium signaling, resulting in dopaminergic neuronal degeneration. It could therefore be proposed that α-syn and LRRK2 play important roles in the mechanisms underlying Ca<sup>2+</sup> dyshomeostasis and excitotoxicity in PD. |
| format | Article |
| id | doaj-art-c87fe65927014d1fb3236af3ea98c5a8 |
| institution | Kabale University |
| issn | 2673-5261 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Journal of Molecular Pathology |
| spelling | doaj-art-c87fe65927014d1fb3236af3ea98c5a82024-12-27T14:32:58ZengMDPI AGJournal of Molecular Pathology2673-52612024-12-015454455710.3390/jmp5040037Effects of Calcium Ion Dyshomeostasis and Calcium Ion-Induced Excitotoxicity in Parkinson’s DiseaseDaleum Nam0Hyejung Kim1Sun Jung Han2Ilhong Son3Dong Hwan Ho4Inam Neuroscience Research Center, Sanbon Medical Center, Wonkwang University, 321, Sanbon-ro, Gunpo-si 15865, Gyeonggi-do, Republic of KoreaInam Neuroscience Research Center, Sanbon Medical Center, Wonkwang University, 321, Sanbon-ro, Gunpo-si 15865, Gyeonggi-do, Republic of KoreaDepartment of Neurology, Sanbon Medical Center, College of Medicine, Wonkwang University, Gunpo-si 15865, Gyeonggi-do, Republic of KoreaInam Neuroscience Research Center, Sanbon Medical Center, Wonkwang University, 321, Sanbon-ro, Gunpo-si 15865, Gyeonggi-do, Republic of KoreaInam Neuroscience Research Center, Sanbon Medical Center, Wonkwang University, 321, Sanbon-ro, Gunpo-si 15865, Gyeonggi-do, Republic of KoreaCalcium ions (Ca<sup>2+</sup>) are vital intracellular messengers that regulate a multitude of neuronal functions, including synaptic transmission, plasticity, exocytosis, and cell survival. Neuronal cell death can occur through a variety of mechanisms, including excitotoxicity, apoptosis, and autophagy. In the context of excitotoxicity, the excessive release of glutamate in the synapses can trigger the activation of postsynaptic receptors. Upon activation, Ca<sup>2+</sup> influx into the cell from the extracellular space via their associated ion channels, most notably L-type Ca<sup>2+</sup> channels. Previous studies have indicated that α-synuclein (α-syn), a typical cytosolic protein, plays a significant role in the pathogenesis of Parkinson’s disease (PD). It is also worth noting that the aggregated form of α-syn has the capacity to affect Ca<sup>2+</sup> homeostasis by altering the function of Ca<sup>2+</sup> regulation. The upregulation of leucine-rich repeat kinase 2 (LRRK2) is closely associated with PD pathogenesis. LRRK2 mutants exhibit a dysregulation of calcium signaling, resulting in dopaminergic neuronal degeneration. It could therefore be proposed that α-syn and LRRK2 play important roles in the mechanisms underlying Ca<sup>2+</sup> dyshomeostasis and excitotoxicity in PD.https://www.mdpi.com/2673-5261/5/4/37Parkinson’s diseaseCa<sup>2+</sup> dyshomeostasisexcitotoxicityα-synucleinleucine-rich repeat kinase 2 |
| spellingShingle | Daleum Nam Hyejung Kim Sun Jung Han Ilhong Son Dong Hwan Ho Effects of Calcium Ion Dyshomeostasis and Calcium Ion-Induced Excitotoxicity in Parkinson’s Disease Journal of Molecular Pathology Parkinson’s disease Ca<sup>2+</sup> dyshomeostasis excitotoxicity α-synuclein leucine-rich repeat kinase 2 |
| title | Effects of Calcium Ion Dyshomeostasis and Calcium Ion-Induced Excitotoxicity in Parkinson’s Disease |
| title_full | Effects of Calcium Ion Dyshomeostasis and Calcium Ion-Induced Excitotoxicity in Parkinson’s Disease |
| title_fullStr | Effects of Calcium Ion Dyshomeostasis and Calcium Ion-Induced Excitotoxicity in Parkinson’s Disease |
| title_full_unstemmed | Effects of Calcium Ion Dyshomeostasis and Calcium Ion-Induced Excitotoxicity in Parkinson’s Disease |
| title_short | Effects of Calcium Ion Dyshomeostasis and Calcium Ion-Induced Excitotoxicity in Parkinson’s Disease |
| title_sort | effects of calcium ion dyshomeostasis and calcium ion induced excitotoxicity in parkinson s disease |
| topic | Parkinson’s disease Ca<sup>2+</sup> dyshomeostasis excitotoxicity α-synuclein leucine-rich repeat kinase 2 |
| url | https://www.mdpi.com/2673-5261/5/4/37 |
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