Neuroscience
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DJ-1 plays a neuroprotective role in cerebral ischemia- reperfusion (I/R) injury and participates in the apoptosis of brain nerve cells, but the underlying mechanism is unclear. We explored the molecular pathways underlying this role using in vivo and in vitro approaches. Middle cerebral artery occlusion- reperfusion (MCAO/R) rat models and oxygen- glucose deprivation- reoxygenation (OGD/R) HAPI cell cultures were used to simulate cerebral ischemia-reperfusion injury. ⋯ In vitro, the Notch1 signaling pathway inhibitor DAPT reversed the neuroprotective effect of ND-13 and promoted apoptosis, weakened the interaction between DJ-1 and Notch1, and decreased the expression of proteins in the Notch1 and Nrf2 pathways. Thus, we found that DJ-1 inhibits apoptosis by regulating the Notch1 signaling pathway and Nrf2 expression in cerebral I/R injury. These results imply that DJ-1 is a potential therapeutic target for cerebral I/R injury.
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Epilepsy is a neurological disorder caused by abnormally elevated neuronal firing and excitability. Spire2, also known as the nucleating factor of F-actin, plays an important role in long-range vesicle transport. This study showed that Spire2 was highly expressed in neurons in the cortex and hippocampus. ⋯ In conclusion, this study revealed a significantly decreased expression of Spire2 in the brain tissues of epileptic individuals and an inhibitory role for this protein in the development of epilepsy. In addition, knockdown of Spire2 aggravated abnormal firing in epileptic mice, while its overexpression had the opposite effect. These findings provide new insights into the mechanism of epileptogenesis.
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Ischaemic stroke (IS) is characterized by high morbidity, disability and mortality and lacks effective solutions. MiRNA-27a has been implicated in ferroptosis, but evidence that miRNA-27a regulates ferroptosis in ischaemic stroke is lacking. Nrf2 could reduce brain tissue injury in ischaemic stroke and resist ferroptosis. ⋯ The results showed that miRNA‑27a inhibited Nrf2 in a targeted manner, which also exacerbated the extent of ferroptosis. However, the miRNA‑27a antagonist reversed the miR‑27a agonist‑mediated effects. Therefore, the present study indicated that miRNA‑27a may aggravate brain tissue ferroptosis during ischaemic stroke, potentially by inhibiting Nrf2.
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Review
The beneficial role of SIRT1 in preventive or therapeutic options of Neurodegenerative Diseases.
Sirtuin 1 (SIRT1) is an NAD+ dependent deacetylase that modify the gene expression through histone deacetylation. SIRT1 plays a crucial role in regulating a wide range of physiological processes by adjustment multiple mechanisms through the deacetylation of multiple substrates. ⋯ Its basic pathogenesis is filamentous tangles and amyloid deposits, such as Amyloid-β (Aβ), tau protein, α-synuclein, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). This summarizes introduces the structure and function of SIRT1, and then analyzes the protective effects of SIRT1 on neurological diseases by regulating circadian rhythm, aging, oxidative stress, mitochondrial dysfunction and neuroinflammation related pathways.
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Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity. ⋯ Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection.