Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zinc is the authoritative metal which is present in our body, and reactive zinc metal is crucial for neuronal signaling and is largely distributed within presynaptic vesicles. Zinc also plays an important role in synaptic function. At cellular level, zinc is a modulator of synaptic activity and neuronal plasticity in both development and adulthood. Different importers and transporters are involved in zinc homeostasis. ZnT-3 is a main transporter involved in zinc homeostasis in the brain. It has been found that alterations in brain zinc status have been implicated in a wide range of neurological disorders including impaired brain development and many neurodegenerative disorders such as Alzheimer's disease, and mood disorders including depression, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and prion disease. Furthermore, zinc has also been implicated in neuronal damage associated with traumatic brain injury, stroke, and seizure. Understanding the mechanisms that control brain zinc homeostasis is thus critical to the development of preventive and treatment strategies for these and other neurological disorders.
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PMID:Zinc: indications in brain disorders. 2565 70

Endoplasmic reticulum (ER) stress has been thought to be involved to neurodegenerative diseases such as Alzheimer's disease (AD) or Amyotrophic lateral sclerosis (ALS). The previous studies have shown that SLC30A3 level is decreased in prefrontal cortex of AD patients. In addition, we have shown that level of zinc (Zn) is increased in cerebrospinal fluid and SLC30A3 level is decreased in spinal cord of ALS patients. It was thought that both SLC30A3 and ER stress could be related to the cause of AD and ALS, however the relationship between ER stress and SLC30A3 has not been elucidated. Therefore we investigated that the role of SLC30A3 against ER stress. The level of SLC30A3 mRNA was significantly increased by tunicamycin treatment in human neuroblastoma cell line (SH-SY5Y) and human embryonic kidney cell line (HEK293). Cell viability under tunicamycin treatment was significantly decreased in SLC30A3 knockdown cells by siRNA in comparison with negative control (NC) cells. Cleaved caspase-3 level was significantly increased in SLC30A3 knockdown cells, not in NC cells. These results showed that SLC30A3 has a protective role to ER stress-induced toxicities. The previous study has shown that SLC30A3 protect cells from oxidative stress in ERK1/2 signal dependent manner, thus we determined the activity of ERK1/2 in SLC30A3 knockdown cells under ER stress condition. The level of ERK1/2 phosphorylation was significantly increased by tunicamycin treatment in NC cells, not in SLC30A3 knockdown cells. The ERK1/2 pathway is thought to have an association with defensive effects of SLC30A3 on cellular stress such as ER stress. In conclusion, this study suggested that SLC30A3 is supposed to play a protective role against ER stress, which is related to ERK1/2 activation.
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PMID:Protective roles of SLC30A3 against endoplasmic reticulum stress via ERK1/2 activation. 2767 94

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease caused by the loss of motor neurons. Although the pathogenesis of sporadic ALS (sALS) remains unclear, it has recently been suggested that disorders of microRNA (miRNA) may be involved in neurodegenerative conditions. The purpose of this study was to investigate miRNA levels in sALS and the target genes of miRNA. Microarray and real-time RT-PCR analyses revealed significantly-decreased levels of miR-139-5p and significantly increased levels of miR-5572 in the spinal cords of sALS patients compared with those in controls. We then focused on miR-5572, which has not been reported in ALS, and determined its target gene. By using TargetScan, we predicted SLC30A3 as the candidate target gene of miR-5572. In a previous study, we found decreased SLC30A3 levels in the spinal cords of sALS patients. We revealed that SLC30A3 was regulated by miR-5572. Taken together, these results demonstrate that the level of novel miRNA miR-5572 is increased in sALS and that SLC30A3 is one of the target genes regulated by miR-5572.
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PMID:MicroRNA-5572 Is a Novel MicroRNA-Regulating SLC30A3 in Sporadic Amyotrophic Lateral Sclerosis. 3259 39