Amyotrophic lateral sclerosis (ALS) is caused by the progressive degeneration of motor neurons in the spinal cord, the brain stem, and the motor cortex. So far, there is still a lack of effective drugs. Nicotinamide adenine dinucleotide (NAD+) takes part in redox reactions and the NAD-dependent signaling pathway. The NAD+ decline is related with many neurological diseases, leading to the accumulation of neurotoxic protein in the central nervous system. Moreover, the NAD+ supplementation is shown to promote neural stem cells/neuronal precursor cells (NSCs/NPCs) pool maintenance. Regulatory mechanisms and functions of NAD+ metabolism in ALS are still unknown. Thus, we hypothesized the aggregation of human SOD1 toxic protein and the fate of NSCs/NPCs in the ALS disease could be improved by the administration of nicotinamide riboside (NR), an NAD+ precursor. In this study, we treated SOD1 G93A transgenic and wild-type mice by the oral administration of 20 mg/ml NR starting at 50 days of age. Effects of NR on the body weight, the motor function, the onset and the survival were assessed during the experiment. The expression of mutant hSOD1 protein, mitochondrial unfolded protein response (UPR mt ) related protein, mitophagy markers and NAD+ metabolism related protein were detected by immunoblotting. Effects of NR on the NSCs/NPCs in neurogenic niches of brain were identified by the immunofluorescence staining. Our investigation elucidated that the NR treatment exhibited better hanging wire endurance but did not postpone the onset or extend the life span of SOD1 G93A mice. Besides, we observed that the NR repletion promoted the clearance of mitochondrial hSOD1 neurotoxic protein. Meanwhile, the mitochondrial function pathway was disrupted in the brain of SOD1 G93A mice. What's more, we demonstrated that the inadequate function of NAD+ salvage synthesis pathway was the primary explanation behind the decline of NAD+, and the NR treatment enhanced the proliferation and migration of NSCs/NPCs in the brain of SOD1 G93A mice. At last, we found that levels of UPR mt related protein were significantly increased in the brain of SOD1 G93A mice after the NR treatment. In summary, these findings reveal that the administration of NR activates UPR mt signaling, modulates mitochondrial proteostasis and improves the adult neurogenesis in the brain of SOD1 G93A mice.
Abstract. Internal carotid artery dissection (ICAD) is a major cause of ischemic stroke in young and middle-aged patients. Patients may be asymptomatic or present with symptoms ranging from headache and neck pain to severe cerebral ischemic events. Conventional treatment is medical anticlotting therapy or involves the use of interventional tools, such as endovascular treatment. Anticoagulation or antiplatelet therapy are the primary treatment modalities used to prevent thromboembolic complications from arterial dissections, however, they are unsuitable in certain cases of dissecting aneurysms. In the current study reports the case of a 52-year-old male patient presenting with the primary complaint of left limb weakness. Computed tomography angiography revealed a right ICAD located in the oropharyngeal segment. Subsequently, digital subtraction angiography was performed to assess the oropharyngeal segment. Antithrombotic therapy resulted in no improvement; therefore, endovascular treatment with the insertion of a Willis covered stent was performed, resulting in an improved outcome.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.