Calcium channel blockers ameliorate disease in a mouse model of multiple sclerosis

Brand-Schieber, Elimor; Werner, Peter

doi:10.1016/j.expneurol.2004.05.023

Cited by 67 publications

(33 citation statements)

References 26 publications

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“…Numerous studies have demonstrated that the calcium ion is critical in the neuronal damage seen in neurodegenerative disease models such as trauma (26), ischemia (27), and EAE (28). Hence, we investigated whether the N-type Ca 2ϩ channel is involved in the pathology of EAE.…”

Section: Discussionmentioning

confidence: 99%

N-type Calcium Channel in the Pathogenesis of Experimental Autoimmune Encephalomyelitis*

Tokuhara

Namiki

Uesugi³

et al. 2010

Journal of Biological Chemistry

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One of the family of voltage-gated calcium channels (VGCC), the N-type Ca 2؉ channel, is located predominantly in neurons and is associated with a variety of neuronal responses, including neurodegeneration. A precise mechanism for how the N-type Ca 2؉ channel plays a role in neurodegenerative disease, however, is unknown. In this study, we immunized N-type Ca . These results suggest that the N-type Ca 2؉ channel is involved in the pathogenesis of EAE at least in part by regulating MCP-1 production by microglia.

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Section: Discussionmentioning

confidence: 99%

N-type Calcium Channel in the Pathogenesis of Experimental Autoimmune Encephalomyelitis*

Tokuhara

Namiki

Uesugi³

et al. 2010

Journal of Biological Chemistry

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“…Diskutiert werden u. a. eine Fehlfunktion verschiedener Ionenkanäle mit nachfolgendem Zusammenbruch der zellulären Energieversorgung und einem übermäßigen (neurotoxischen) Anstieg der intrazellulären Ca 2+ -Konzentration. Zudem sollen exzitatorische Neurotransmitter wie beispielsweise das Glutamat vermehrt in der weißen Substanz ausgeschüttet werden [36]. Darüber hinaus wird eine Vielzahl weiterer Mechanismen angeführt, durch welche das Axon potenziell geschädigt werden kann (siehe Abschnitt "Neuroprotektion und Neuroregeneration").…”

Section: Heterogenität Und Neurodegeneration In Ms-läsionenunclassified

“…Die subzelluläre Verteilung dieser Untereinheit innerhalb der axonalen Membran entsprach dem des β-Amyloid-Vorläufer-proteins (APP), das ein früher und empfindlicher Marker für eine Beeinträchti-gung des axonalen Transports ist [114]. Darüber hinaus konnten pharmakologische Inhibitoren von spannungsaktivierten L-Typ-Ca 2+ -Kanälen wie Bepridil und Nitrendipin günstige Effekte auf Dauer und Schwere der EAE vermitteln [36].…”

Section: Kalziumkanäleunclassified

Update on pathophysiologic and immunotherapeutic approaches for the treatment of multiple sclerosis

et al. 2007

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Multiple sclerosis (MS) is a chronic disabling disease with significant implications for patients and society. The individual disease course is difficult to predict due to the heterogeneity of clinical presentation and of radiologic and pathologic findings. Although its etiology still remains unknown, the last decade has brought considerable understanding of the underlying pathophysiology of MS. In addition to its acceptance as a prototypic inflammatory autoimmune disorder, recent data reveal the importance of primary and secondary neurodegenerative mechanisms such as oligodendrocyte death, axonal loss, and ion channel dysfunction. The deepened understanding of its immunopathogenesis and the limited effectiveness of currently approved disease-modifying therapies have led to a tremendous number of trials investigating potential new drugs. Emerging treatments take into account the different immunopathological mechanisms and strategies, to protect against axonal damage and promote remyelination. This review provides a compilation of novel immunotherapeutic strategies and recently uncovered aspects of known immunotherapeutic agents. The pathogenetic rationale of these novel drugs for the treatment of MS and accompanying preclinical and clinical data are highlighted.

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“…In a study of EAE-affected rats, the effect of bepridil, a broad-spectrum Ca 2+ channel blocker, was compared with nitrendipine, which is a blocker of l-type VGCCs. Both drugs prevented axonal loss and disablity in treated animals [126]. However, clinical trials in MS patients are not available at the moment.…”

Section: Promising Therapeutic Concepts With Putative Neuroprotectivementioning

confidence: 99%

Neurodegeneration in multiple sclerosis: novel treatment strategies

Luessi

Siffrin

Zipp³

2012

Expert Review of Neurotherapeutics

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In recent years it has become clear that the neuronal compartment already plays an important role early in the pathology of multiple sclerosis (MS). Neuronal injury in the course of chronic neuroinflammation is a key factor in determining long-term disability in patients. Viewing MS as both inflammatory and neurodegenerative has major implications for therapy, with CNS protection and repair needed in addition to controlling inflammation. Here, the authors' review recently elucidated molecular insights into inflammatory neuronal/axonal pathology in MS and discuss the resulting options regarding neuroprotective and regenerative treatment strategies. Neurodegeneration in multiple sclerosis: novel treatment strategiesExpert Rev. Neurother. 12(9), 1061-1077 (2012) Keywords: multiple sclerosis • neurodegeneration • neuronal injury • neuroprotection • treatment Medscape: Continuing Medical Education OnlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Expert Reviews Ltd. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians.Medscape, LLC designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at www.medscape.org/journal/expertneurothera; (4) view/print certificate. Learning objectivesUpon completion of this activity, participants will be able to:• Describe recent insights into inflammatory neuronal injury in multiple sclerosis, based on a review • Describe methods of quantification of neuronal injury in patients with multiple sclerosis, based on a review • Describe applications of these findings to treatment for patients with multiple sclerosis, based on a review

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Calcium channel blockers ameliorate disease in a mouse model of multiple sclerosis

Cited by 67 publications

References 26 publications

N-type Calcium Channel in the Pathogenesis of Experimental Autoimmune Encephalomyelitis*

N-type Calcium Channel in the Pathogenesis of Experimental Autoimmune Encephalomyelitis*

Update on pathophysiologic and immunotherapeutic approaches for the treatment of multiple sclerosis

Neurodegeneration in multiple sclerosis: novel treatment strategies

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