Zonisamide up-regulated the mRNAs encoding astrocytic anti-oxidative and neurotrophic factors

Choudhury, ME; Sugimoto, Keishi; Kubo, Madoka; Iwaki, Hirotaka; Tsujii, Tomoaki; Kyaw, Win Thiri; Nishikawa, Noriko; Nagai, Masahiro; Tanaka, Junya; Nomoto, Masahiro

doi:10.1016/j.ejphar.2012.05.012

Cited by 24 publications

(28 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro and in vivo evidence in 6-OHDA, MPTP and rotenone models; dose-dependent neuroprotection of DA neurons in 6-OHDA, MPTP and rotenone models in vivo and in vitro, albeit with conflicting doses 46,[205][206][207] Symptomatic improvement in motor function in an RCT 208…”

Section: Calcium Channel Blockadementioning

confidence: 99%

The ongoing pursuit of neuroprotective therapies in Parkinson disease

2014

View full text Add to dashboard Cite

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD.

show abstract

Section: Calcium Channel Blockadementioning

confidence: 99%

The ongoing pursuit of neuroprotective therapies in Parkinson disease

2014

View full text Add to dashboard Cite

show abstract

“…Although MT-1/-2 can protect neurons directly, they are not mainly expressed in neurons in the normal or injured state [60, 61]. There are a number of evidences demonstrating that MT-1/-2 are produced primarily by astrocytes [62-73], and that extracellular MTs secreted from astrocytes mediate neuronal survival and axonal regeneration [60]. Michael et al [64] reported up-regulation of MT expression in reactive astrocytes of the substantia nigra in PD patients, suggesting a neuroprotective role for dopaminergic neurons.…”

Section: Neuroprotective Properties Of Astrocytes In Parkinson's Diseasementioning

confidence: 99%

Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease

Miyazaki

Asanuma²

2016

CMC

View full text Add to dashboard Cite

Astrocytes are the most abundant neuron-supporting glial cells in the central nervous system. The neuroprotective role of astrocytes has been demonstrated in various neurological disorders such as amyotrophic lateral sclerosis, spinal cord injury, stroke and Parkinson’s disease (PD). Astrocyte dysfunction or loss-of-astrocytes increases the susceptibility of neurons to cell death, while astrocyte transplantation in animal studies has therapeutic advantage. We reported recently that stimulation of serotonin 1A (5-HT1A) receptors on astrocytes promoted astrocyte proliferation and upregulated antioxidative molecules to act as a neuroprotectant in parkinsonian mice. PD is a progressive neurodegenerative disease with motor symptoms such as tremor, bradykinesia, rigidity and postural instability, that are based on selective loss of nigrostriatal dopaminergic neurons, and with non-motor symptoms such as orthostatic hypotension and constipation based on peripheral neurodegeneration. Although dopaminergic therapy for managing the motor disability associated with PD is being assessed at present, the main challenge remains the development of neuroprotective or disease-modifying treatments. Therefore, it is desirable to find treatments that can reduce the progression of dopaminergic cell death. In this article, we summarize first the neuroprotective properties of astrocytes targeting certain molecules related to PD. Next, we review neuroprotective effects induced by stimulation of 5-HT1A receptors on astrocytes. The review discusses new promising therapeutic strategies based on neuroprotection against oxidative stress and prevention of dopaminergic neurodegeneration.

show abstract

“…However, similar to in vitro studies, it was unclear whether this neuroprotection in vivo was due to blocking of T-type calcium channels or regulating other signaling pathways. It is possible that these blockers act on oxidative, neurotrophic, or both pathways to protect auditory neurons against acoustic trauma [14]. …”

Section: Neuroprotection Evidence From In Vitro and In Vivo Modelsmentioning

confidence: 99%

“…It can upregulate mRNA for astrocyte-derived neurotrophic factor VEGF providing neuroprotection [14] (Figure 2 Pathway 7). During a hyperexcitable state, zonisamide inhibits both GABA and glutamate and also prevents calcium overload by suppressing ryanodine [81] (Figure 2 Pathway 8).…”

Section: Neuroprotective Mechanisms Of T-type Calcium Channelsmentioning

confidence: 99%

T-type calcium channel blockers as neuroprotective agents

Kopecky

Liang

Bao

2014

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

T-type calcium channels are expressed in many diverse tissues, including neuronal, cardiovascular, and endocrine. T-type calcium channels are known to play roles in the development, maintenance, and repair of these tissues but have also been implicated in disease when not properly regulated. Calcium channel blockers have been developed to treat various diseases and their use clinically is widespread due to both their efficacy as well as their safety. Aside from their established clinical applications, recent studies have suggested neuroprotective effects of T-type calcium channels blockers. Many of the current T-type calcium channel blockers could act on other molecular targets besides T-type calcium channels making it uncertain whether their neuroprotective effects are solely due to blocking of T-type calcium channels. In this review, we discuss these drugs as well as newly developed chemical compounds that are designed to be more selective for T-type calcium channels. We review in vitro and in vivo evidence of neuroprotective effects by these T-type calcium channel blockers. We conclude by discussing possible molecular mechanisms underlying neuroprotective effects by T-type calcium channel blockers.

show abstract

Zonisamide up-regulated the mRNAs encoding astrocytic anti-oxidative and neurotrophic factors

Cited by 24 publications

References 46 publications

The ongoing pursuit of neuroprotective therapies in Parkinson disease

The ongoing pursuit of neuroprotective therapies in Parkinson disease

Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease

T-type calcium channel blockers as neuroprotective agents

Contact Info

Product

Resources

About