The Role of Striatal Cav1.3 Calcium Channels in Therapeutics for Parkinson’s Disease

Caulfield, Margaret E.; Manfredsson, Fredric P.; Steece‐Collier, Kathy

doi:10.1007/164_2022_629

Cited by 3 publications

(1 citation statement)

References 121 publications

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“…In the presence of DA depletion and reduced inhibitory action of D2 receptors, Ca V 1.3 channels are “disinhibited”, promoting increases in intraspinous Ca 2+ through an increase in Ca 2+ transients mediated by readily opened Ca V 1.3 channels resulting in spine retraction ( Day et al, 2006 ). There remains controversy as to whether striatal DA depletion results in spine loss specifically in SPNs of D2 receptor containing indirect pathway or whether it occurs in SPNs of both indirect and direct pathway (for review ( Bastide and Bezard, 2015 ; Caulfield et al, 2023 )). Silencing Ca V 1.3 channel activity, either pharmacologically ( Schuster et al, 2009 ; Soderstrom et al, 2010 ) or with shRNA gene therapy ( Steece-Collier et al, 2019 ) results in amelioration of LID, seemingly related to protection against D2 mediated mechanisms of spine loss and associated aberrant synaptic plasticity.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of striatal CaV1.3 inhibits the escalation of levodopa-induced dyskinesia in male and female parkinsonian rats of advanced age

Caulfield¹,

Werp²,

Stancati³

et al. 2023

Neurobiology of Disease

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Section: Discussionmentioning

confidence: 99%

Downregulation of striatal CaV1.3 inhibits the escalation of levodopa-induced dyskinesia in male and female parkinsonian rats of advanced age

Caulfield¹,

Werp²,

Stancati³

et al. 2023

Neurobiology of Disease

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Customized treatment for Parkinson’s disease: extending lifespan and improving symptoms

Indu,

Dimri

2024

Egypt J Neurol Psychiatry Neurosurg

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Background Parkinson's disease (PD) is the second most prevalent neurodegenerative ailment affecting aged people. Several motor and non-motor symptoms appearing with this disease are linked to reduction in dopamine levels. Parkinson’s disease manifested by a wide range of symptoms, including gait instability, voice impairments, bradykinesia, hypomimia, tremors, and cognitive dysfunctions, where the concern is its steady global progression. Therefore, by evaluating the stage-specific retention and transition thresholds, the suggested work attempts to detect the progression of PD. Similarly, the assessment of the annual rate of deterioration of symptoms aids in assessing the influence of medications on four stages and six prime symptoms. Results During the 9-year period following clinical diagnosis, a symptomatic deterioration of 34.995% is observed in untreated patients compared to treated patients. Furthermore, the experimental analysis illustrates that medicines assist in regulating only bradykinesia, tremors, hypomimia, and speech impairment, which lasts for 4.8 years on average. A saturation period is also identified during the moderate phase, where the computed average depreciation in the Unified Parkinson’s Disease Rating Scale (UPDRS) is the least. Similarly, from stages 1 to 4, medicines might improve stage retention by 4.44, 3.5, 2.72, and 1.6 years, respectively. It demonstrates that, despite transient advantages and adverse effects, medications also have an optimistic impact on PD patients. Conclusions Here, we show that medication can extend the lifespan of PD patients up to 12 years cumulatively. Furthermore, the proposed work suggests that stagewise alternative remedies for improving quality of life, boosting the benefits of medicines, and eliminating their side effects. These include counselling, diet changes, yoga asanas, herbal medicines, bio-cleansing and other therapies. The current work does not consider the temporary transition among stages; nonetheless, further investigation regarding PD could open avenues for more worthy treatments with fewer side effects.

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Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

Qiu,

Yang,

Gong

et al. 2024

Neural Regeneration Research

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The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channel- specific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood-brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.

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The Role of Striatal Cav1.3 Calcium Channels in Therapeutics for Parkinson’s Disease

Cited by 3 publications

References 121 publications

Downregulation of striatal CaV1.3 inhibits the escalation of levodopa-induced dyskinesia in male and female parkinsonian rats of advanced age

Downregulation of striatal CaV1.3 inhibits the escalation of levodopa-induced dyskinesia in male and female parkinsonian rats of advanced age

Customized treatment for Parkinson’s disease: extending lifespan and improving symptoms

Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

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