Mitophagy in neurodegenerative disease pathogenesis

Mitochondria are critical cellular energy resources and are central to the life of the neuron.Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis.Mature neurons are postmitotic and consume substantial energy,thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria.Recent evidence indicates that mitophagy is pivotal to the pathogenesis of neurological diseases.However,more work is needed to study mitophagy pathway components as potential therapeutic targets.In this review,we briefly discuss the characteristics of nonselective autophagy and selective autophagy,including ERphagy,aggrephagy,and mitophagy.We then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological conditions.Next,we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate mitophagy.Importantly,we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.Last,we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative diseases.Together,our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.

Clinical Effect of Intelligent Emergency Nursing Mode in Patients with Severe Traumatic Brain Injury

Objective: Severe traumatic brain injury (sTBI) is one of the common acute and critical diseases in neurosurgery. So we aim to explore the clinical effectiveness of an intelligent emergency care model in patients with severe traumatic brain injury. Methods: Eighty patients with severe traumatic brain injury (sTBI) who were treated in Zhuji People’s Hospital of Zhejiang Province from January 2019 to December 2021 were selected as the study subjects. The patients were divided into an observation group and a control group with 40 patients in each group according to the random number table method. Patients in the control group received conventional first-aid nursing mode intervention, and the intelligent emergency nursing mode was used for the observation group based on the control group. Comparisons were conducted between the two groups on the time of arrival to the emergency room, the time from the emergency room to the operating room, Glasgow Coma Scale (GCS) score before surgery, GCS score when leaving the Intensive Care Unit (ICU), the average length of ICU stay, the average length of hospital stay, the total hospital costs. Results: The time of arrival to the emergency room, the time from the emergency room to the operating room, the average length of ICU stay, the average length of hospital stay, and the total hospital costs in the observation group were significantly lower than those in the control group, and the differences were statistically significant (All P Conclusion: Intelligent emergency nursing mode can shorten the time of sTBI rescue, the length of ICU stay, and the average length of hospital stay, reduce the total hospitalization cost, improve the prognosis, with good efficacy, reduce the total cost of hospitalization, and improve the prognosis with better efficacy.

Functional Recovery with Electro-Acupuncture Stimulation in an Mecp2-Knockout Rat Model of Rett Syndrome

Rett syndrome is a progressive neurodevelopmental disorder that lacks effective treatments.Although deep-brain stimulation can alleviate some symptoms in Rett model mice,this interventional manipula-tion requires deliberate surgical operations.Here,we report that electro-acupuncture stimulation(EAS)can ameliorate symptoms of an Mecp2-knockout rat model of Rett syndrome from the remote acupoints Baihui(GV 20),Yongquan(KI 1),and Shenmen(HT 7).We find that EAS not only prolongs the survival time of Rett rats,but also improves their behavior ability,including locomotion,motor coordination,and social interaction.Neural activation was observed in the substantia nigra of the midbrain,corpus striatum,and cerebral cortex of wild-type and Rett model rats,as reflected by the increased expression of the c-Fos protein.Hence,EAS provides a potential promising therapeutic tool for treating neurodevel-opmental diseases.

Extension of the Lifespan of a Mouse Model of Rett Syndrome by Intracerebroventricular Delivery of MECP2

DearEditors,Rett Syndrome(RTT)is a severe neurodevelopmental disorder characterized by neural dysfunctions and a reduced lifespan,mainly in female patients,involving loss-of-function mutations in the methyl-CpG binding protein 2(MECP2)gene[1-4].

Combining Residual Attention Mechanisms and Generative Adversarial Networks for Hippocampus Segmentation

This research discussed a deep learning method based on an improved generative adversarial network to segment the hippocampus.Different convolutional configurations were proposed to capture information obtained by a segmentation network.In addition,a generative adversarial network based on Pixel2Pixel was proposed.The generator was a codec structure combining a residual network and an attention mechanism to capture detailed information.The discriminator used a convolutional neural network to discriminate the segmentation results of the generated model and that of the expert.Through the continuously transmitted losses of the generator and discriminator,the generator reached the optimal state of hippocampus segmentation.T1-weighted magnetic resonance imaging scans and related hippocampus labels of 130 healthy subjects from the Alzheimer’s disease Neuroimaging Initiative dataset were used as training and test data;similarity coefficient,sensitivity,and positive predictive value were used as evaluation indicators.Results showed that the network model could achieve an efficient automatic segmentation of the hippocampus and thus has practical relevance for the correct diagnosis of diseases,such as Alzheimer’s disease.

Loss of CREST leads to neuroinflammatory responses and ALS-like motor defects in mice

Background:Amyotrophic lateral sclerosis(ALS)is a late onset neurodegenerative disease with fast progression.ALS has heavy genetic components in which a series of genetic mutations have been identified.In 2013,Mutations of the CREST gene(also known as SS18L1),which functions as a calcium-regulated transcriptional activator,were found in sporadic ALS patients.However,the pathogenic causality and mechanisms of ALS-associated mutations of CREST remain to be determined.Methods:In this study,we constructed CREST knockout and Q394X knock-in mice with CRISPR/Cas9 system.Using biochemical and imaging tools,we illustrated core pathological phenotypes in CREST mutant mice and claimed the possible pathogenic mechanisms.Furthermore,we also observed locomotion defects in CREST mutant mice with behavioural tests.Results:We demonstrate that ALS-related CREST-Q388X mutation exhibits loss-of-function effects.Importantly,the microglial activation was prevalent in CREST haploinsufficiency mice and Q394X mice mimicking the human CREST Q388X mutation.Furthermore,we showed that both CREST haploinsufficiency and Q394X mice displayed deficits in motor coordination.Finally,we identified the critical role of CREST-BRG1 complex in repressing the expression of immune-related cytokines including Ccl2 and Cxcl10 in neurons,via histone deacetylation,providing the molecular mechanisms underlying inflammatory responses within mice lack of CREST.Conclusion:Our findings indicate that elevated inflammatory responses in a subset of ALS may be caused by neuron-derived factors,suggesting potential therapeutic methods through inflammation pathways.