Journal of pharmacological sciences
-
Botulinum toxin type A is a unique candidate for inhibition of pain transmission. In the present study we attempted to see the beneficial actions of A2 neurotoxin (NTX), an active subunit of botulinum toxin type A. ⋯ Spinal application of A2 NTX also showed a potent suppression of thermal hyperalgesia and mechanical allodynia in the spinal cord injury-induced neuropathic pain model. A2 NTX seems to be a long-lasting treatment for diabetic and spinal cord injury-induced neuropathic pain.
-
Alzheimer's disease (AD) is a neurodegenerative disease of the brain associated with irreversible cognitive decline, memory impairment, and behavioral changes. Postmortem brains of AD patients reveal neuropathologic features, in particular the presence of senile plaques (SPs) and neurofibrillary tangles (NFTs), which contain β-amyloid peptides and highly phosphorylated tau proteins. Currently, AD can only be definitively confirmed by postmortem histopathologic examination of SPs and NFTs in the brain. ⋯ Several of the PET probes have been shown in clinical trials to be useful for the imaging of β-amyloid plaques in living brain tissue. More recently, the development of PET/SPECT probes for in vivo imaging of NFTs is an active area of study in the field of molecular imaging because the appearance of NFT pathology correlates well with clinical severity of dementia. We will review current research on the development of PET/SPECT imaging probes for in vivo detection of SPs and NFTs and their application to diagnosis and therapy of AD.
-
Neurosteroids are known as allosteric modulators of the ligand-gated ion channel superfamily. Voltage-gated sodium channels (Na(v)) play an important role in mediating excitotoxic damages. ⋯ The suppression of I(Na) by pregnenolone sulphate was due to increased inactivation with little change in activation. These findings suggest that pregnenolone sulphate, a metabolite of pregnenolone, suppresses the function of Na(v) via increased inactivation, which may contribute to the neuroprotection.
-
Peripheral neuropathic pain is a serious side effect of paclitaxel treatment. However, the mechanism of this paclitaxel-induced neuropathic pain is unknown. In this study, we investigated the effects of paclitaxel on the voltage-dependent calcium channel (VDCC) current in rat dorsal root ganglion (DRG) neurons using the whole-cell patch clamp technique. ⋯ Immunohistochemistry showed that paclitaxel treatment increased Ca(v)α₂δ-1 protein expression in DRG neurons. Thus, paclitaxel treatment increases the VDCC current in small- and medium-diameter DRG neurons and upregulates Ca(v)α₂δ-1. The antihyperalgesic action of gabapentin may be due to inhibition of paclitaxel-induced increases in the VDCC current in DRG neurons.
-
Pathological hallmarks of Alzheimer's disease (AD) include senile plaques, neurofibrillary tangles (NFTs), synaptic loss, and neurodegeneration. Senile plaques are composed of amyloid-β (Aβ) and are surrounded by microglia, a primary immune effector cell in the central nervous system. NFTs are formed by the intraneuronal accumulation of hyperphosphorylated tau, and progressive synaptic and neuronal losses closely correlate with cognitive deficits in AD. ⋯ Although details of the interaction between AD pathologies remain unclear, experimental evidences to discuss this issue have been accumulated. In this paper, we review and discuss recent findings that link the AD pathologies to each other. Further studies on the interaction between pathologies induced in AD brain may contribute to provide deep insight into the pathogenesis of AD and to develop novel therapeutic, prophylactic, and early diagnostic strategies for AD.