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OBJECTIVE: Proteomic elucidation is an essential step in improving our understanding of the biological properties of proteins in amyotrophic lateral sclerosis (ALS). METHODS: Preliminary proteomic analysis was performed on the spinal cord and brain of SOD1 G93A (TG) and wild-type (WT) mice using isobaric tags for relative and absolute quantitation. RESULTS: Partial up- and downregulated proteins showing significant differences between TG and WT mice were identified, of which 105 proteins overlapped with differentially expressed proteins in both the spinal cord and brain of progression mice. Bioinformatic analyses using Gene Ontology, a cluster of orthologous groups, and Kyoto Encyclopedia of Genes and Genomes pathway revealed that the significantly up- and downregulated proteins represented multiple biological functions closely related to ALS, with 105 overlapping differentially expressed proteins in the spinal cord and brain at the progression stage of TG mice closely related to 122 pathways. Differentially expressed proteins involved in a set of molecular functions play essential roles in maintaining neural cell survival. CONCLUSION: This study provides additional proteomic profiles of TG mice, including potential overlapping proteins in both the spinal cord and brain that participate in pathogenesis, as well as novel insights into the up- and downregulation of proteins involved in the pathogenesis of ALS.
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Amyotrophic lateral sclerosis (ALS) currently lacks the useful diagnostic biomarkers. The current diagnosis of ALS is mainly depended on the clinical manifestations, which contributes to the diagnostic delay and be difficult to make the accurate diagnosis at the early stage of ALS, and hinders the clinical early therapeutics. The more and more pathogenesis of ALS are found at the last 30â¯years, including excitotoxicity, the oxidative stress, the mitochondrial dysfunction, neuroinflammation, the altered energy metabolism, the RNA misprocessing and the most recent neuroimaging findings. The findings of these pathogenesis bring the new clues for searching the diagnostic biomarkers of ALS. At present, a large number of relevant studies about the diagnostic biomarkers are underway. The ALS pathogenesis related to the diagnostic biomarkers might lessen the diagnostic reliance on the clinical manifestations. Among them, the cortical altered signatures of ALS patients derived from both structural and functional magnetic resonance imaging and the emerging proteomic biomarkers of neuronal loss and glial activation in the cerebrospinal fluid as well as the potential biomarkers in blood, serum, urine, and saliva are leading a new phase of biomarkers. Here, we reviewed these current potential diagnostic biomarkers of ALS.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease mainly characterized by the accumulation of ubiquitinated proteins in the affected motor neurons. At present, the accurate pathogenesis of ALS remains unclear and there are still no effective treatment measures for ALS. The potential pathogenesis of ALS mainly includes the misfolding of some pathogenic proteins, the genetic variation, mitochondrial dysfunction, autophagy disorders, neuroinflammation, the misregulation of RNA, the altered axonal transport, and gut microbial dysbiosis. Exploring the pathogenesis of ALS is a critical step in searching for the effective therapeutic approaches. The current studies suggested that the genetic variation, gut microbial dysbiosis, the activation of glial cells, and the transportation disorder of extracellular vesicles may play some important roles in the pathogenesis of ALS. This review conducts a systematic review of these current potential promising topics closely related to the pathogenesis of ALS; it aims to provide some new evidences and clues for searching the novel treatment measures of ALS.
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Amyotrophic lateral sclerosis (ALS) is a debilitating motor neurological disorder for which there is still no cure. The disease seriously jeopardizes the health and lifespan of adult populations. The authors extensively retrieved the current literature about clinical and experimental ALS treatments. Based on them, this review primarily focused on summarizing the current potential clinical usage and trialing therapeutics of ALS. Currently, the clinical ALS treatments have focused primarily on relieving symptoms to improve the quality of life yet. There are a number of therapeutic approaches such as medicine, gene therapy, neuron protectants, combination therapy and stem cells. Among them, Stem cells including embryonic stem cells, mesenchymal stem cells, neural stem cells, and many other types of stem cells have been used in ALS treatment, and although the short-term efficacy is good, it is worth exploring whether this improved efficacy leads to prolonged patient survival. In addition, the supportive treatments also exert an important effect on improving the quality of life and prolong the survival of ALS patients in absence of effectively care for stopping or reversing the progression of ALS.
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Amyotrophic lateral sclerosis is a fatal, multigenic, multifactorial neurodegenerative disease characterized by upper and lower motor neuron loss. Animal models are essential for investigating pathogenesis and reflecting clinical manifestations, particularly in developing reasonable prevention and therapeutic methods for human diseases. Over the decades, researchers have established a host of different animal models in order to dissect amyotrophic lateral sclerosis (ALS), such as yeast, worms, flies, zebrafish, mice, rats, pigs, dogs, and more recently, non-human primates. Although these models show different peculiarities, they are all useful and complementary to dissect the pathological mechanisms of motor neuron degeneration in ALS, contributing to the development of new promising therapeutics. In this review, we describe several common animal models in ALS, classified by the naturally occurring and experimentally induced, pointing out their features in modeling, the onset and progression of the pathology, and their specific pathological hallmarks. Moreover, we highlight the pros and cons aimed at helping the researcher select the most appropriate among those common experimental animal models when designing a preclinical ALS study.
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Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by the progressive death of motor neurons in the cerebral cortex, brain stem, and spinal cord. The exact mechanisms underlying the pathogenesis of ALS remain unclear. The current consensus regarding the pathogenesis of ALS suggests that the interaction between genetic susceptibility and harmful environmental factors is a promising cause of ALS onset. The investigation of putative harmful environmental factors has been the subject of several ongoing studies, but the use of transgenic animal models to study ALS has provided valuable information on the onset of ALS. Here, we review the current common invertebrate genetic models used to study the pathology, pathophysiology, and pathogenesis of ALS. The considerations of the usage, advantages, disadvantages, costs, and availability of each invertebrate model will also be discussed.
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JOURNAL/nrgr/04.03/01300535-202419110-00031/figure1/v/2024-03-08T184507Z/r/image-tiff Amyotrophic lateral sclerosis is a neurodegenerative disease, and the molecular mechanism underlying its pathology remains poorly understood. However, inflammation is known to play an important role in the development of this condition. To identify driver genes that affect the inflammatory response in amyotrophic lateral sclerosis, as well as potential treatment targets, it is crucial to analyze brain tissue samples from patients with both sporadic amyotrophic lateral sclerosis and C9orf72-related amyotrophic lateral sclerosis. Therefore, in this study we used a network-driven gene analysis tool, NetBID2.0, which is based on SJARACNe, a scalable algorithm for the reconstruction of accurate cellular networks, to experimentally analyze sequencing data from patients with sporadic amyotrophic lateral sclerosis. The results showed that the OSMR gene is pathogenic in amyotrophic lateral sclerosis and participates in the progression of amyotrophic lateral sclerosis by mediating the neuroinflammatory response. Furthermore, there were differences in OSMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral sclerosis. These findings suggest that OSMR may be a diagnostic and prognostic marker for amyotrophic lateral sclerosis.
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Cognitive impairment (CI) is a common complication of the non-motor symptoms in Parkinson's disease (PD), including PD with mild cognitive impairment (PD-MCI) and PD dementia. Recent studies reported the oral dysbiosis in PD and CI, respectively. Porphyromonas gingivalis (P. gingivalis), a pathogen of oral dysbiosis, plays an important role in PD, whose lysine-gingipain (Kgp) could lead to AD-type pathologies. No previous study investigated the composition of oral microbiota and role of P. gingivalis in PD-MCI. This study aimed to investigate the differences of oral microbiota composition, P. gingivalis copy number, and Kgp genotypes among PD-MCI, PD with normal cognition (PD-NC) and periodontal status-matched control (PC) groups. The oral bacteria composition, the copy number of P. gingivalis, and the Kgp genotypes in gingival crevicular fluid from PD-MCI, PD-NC, and PC were analyzed using 16S ribosomal RNA sequencing, quantitative real-time PCR, and MseI restriction. We found that the structures of oral microbiota in PD-MCI group were significantly different compared to that in PD-NC and PC group. The relative abundances of Prevotella, Lactobacillus, Megasphaera, Atopobium, and Howardella were negatively correlated with cognitive score. Moreover, there was a significant difference of Kgp genotypes among the three groups. The predominant Kgp genotypes of P. gingivalis in the PD-MCI group were primarily Kgp II, whereas in the PD-NC group, it was mainly Kgp I. The Kgp II correlated with lower MMSE and MoCA scores, which suggested that Kgp genotypes II is related to cognitive impairment in PD.
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Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease which damages upper and lower motor neurons (UMN and LMN) innervating the muscles of the trunk, extremities, head, neck and face in cerebrum, brain stem and spinal cord, which results in the progressive weakness, atrophy and fasciculation of muscle innervated by the related UMN and LMN, accompanying with the pathological signs leaded by the cortical spinal lateral tract lesion. The pathogenesis about ALS is not fully understood, and no specific drugs are available to cure and prevent the progression of this disease at present. In this review, we reviewed the structure and associated functions of copper-zinc superoxide dismutase 1 (SOD1), discuss why SOD1 is crucial to the pathogenesis of ALS, and outline the pathogenic mechanisms of SOD1 in ALS that have been identified at recent years, including glutamate-related excitotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, axonal transport disruption, prion-like propagation, and the non-cytologic toxicity of glial cells. This review will help us to deeply understand the current progression in this field of SOD1 pathogenic mechanisms in ALS.
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Esclerose Lateral Amiotrófica , Superóxido Dismutase-1 , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/genética , Humanos , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/genética , Animais , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Estresse Oxidativo/fisiologiaRESUMO
INTRODUCTION: Recently, chloride channel CLIC-like 1 (CLCC1) was reported to be a novel ALS-related gene. We aimed to screen CLCC1 variants in our ALS cohort and further explore the genotype-phenotype correlation of CLCC1-related ALS. METHODS: We screened rare damaging variants in CLCC1 from our cohorts of 1005 ALS patients and 1224 healthy controls with whole-exome sequencing in Central South China. Fisher's exact test was conducted for association analysis at the entire gene level and single variant level. RESULTS: In total, four heterozygous missense variants in CLCC1 were identified from four unrelated sporadic ALS patients and predicted to be putative pathogenic by in silico tools and protein model prediction, accounting for 0.40% of all patients (4/1005). The four variants were c.A275C (p.Q92P), c.G1139A (p.R380K), c.C1244T (p.T415M), and c.G1328A (p.R443Q), respectively, which had not been reported in ALS patients previously. Three of four variants were located in exon 10. Patients harboring CLCC1 variants seemed to share a group of similar clinical features, including earlier age at onset, rapid progression, spinal onset, and vulnerable cognitive status. Statistically, we did not find CLCC1 to be associated with the risk of ALS at the entire gene level or single variant level. CONCLUSION: Our findings further expanded the genetic and clinical spectrum of CLCC1-related ALS and provided more genetic evidence for anion channel involvement in the pathogenesis of ALS, but further investigations are needed to verify our findings.
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Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/genética , Mutação , Mutação de Sentido Incorreto , Estudos de Associação Genética , China , Canais de Cloreto/genéticaRESUMO
Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system, the cause of which remains unexplained despite several years of research. Thus, the journey to understanding or treating amyotrophic lateral sclerosis is still a long one. According to current research, amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways. The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis. Here, we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis, as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis. In addition, we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis. Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.
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OBJECTIVE: To investigate the alteration of PV interneurons in ALS mainly focusing its dynamic changes and its relationship with motor neurons and ErbB4 signaling. METHODS: SOD1G93A mice were used as ALS model. ALS animals were divided into different groups according to birth age: symptomatic prophase (50~60 days), symptomatic phase (90~100 days), and symptomatic progression (130~140 days). Immunofluorescence was performed for measurement of PV-positive interneurons, MMP-9, ChAT, NeuN and ErbB4. RT-qPCR and western blot were used to determine the expression of PV and MMP-9. RESULTS: PV expression was remarkably higher in the anterior horn of gray matter compared with posterior horn and area in the middle of gray matter in control mice. In ALS mice, PV, MMP-9 and ErbB4 levels were gradually decreased along with onset. PV, MMP-9 and ErbB4 levels in ALS mice were significantly down-regulated than control mice after onset, indicating the alteration of PV interneurons, FαMNs and ErbB4. SαMNs levels only decreased remarkably at symptomatic progression in ALS mice compared with control mice, while γMNs levels showed no significant change during whole period in all mice. MMP-9 and ErbB4 were positively correlated with PV. NRG1 treatment significantly enhanced the expression of ErBb4, PV and MMP-9 in ALS mice. CONCLUSION: PV interneurons decrease is along with FαMNs and ErbB4 decrease in ALS mice.
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Esclerose Lateral Amiotrófica , Interneurônios , Animais , Camundongos , Esclerose Lateral Amiotrófica/metabolismo , Interneurônios/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Transgênicos , Parvalbuminas/metabolismo , Receptor ErbB-4/genética , Receptor ErbB-4/metabolismo , Neuregulina-1/genética , Neuregulina-1/metabolismoRESUMO
Amyotrophic Lateral Sclerosis (ALS) is one of the commonest neurodegenerative diseases of adult-onset, which is characterized by the progressive death of motor neurons in the cerebral cortex, brain stem and spinal cord. The dysfunction and death of motor neurons lead to the progressive muscle weakness, atrophy, fasciculations, spasticity and ultimately the whole paralysis of body. Despite the identification of several genetic mutations associated with the pathogenesis of ALS, including mutations in chromosome 9 open reading frame 72 leading to the abnormal expansion of GGGGCC repeat sequence, TAR DNA-binding protein 43, fused in sarcoma/translocated in liposarcoma, copper/zinc superoxide dismutase 1 (SOD1) and TANK-binding kinase 1, the exact mechanisms underlying the specific degeneration of motor neurons that causes ALS remain incompletely understood. At present, since the transgenic model expressed SOD1 mutants was established, multiple in vitro models of ALS have been developed for studying the pathology, pathophysiology and pathogenesis of ALS as well as searching the effective neurotherapeutics. This review reviewed the details of present established in vitro models used in studying the pathology, pathophysiology and pathogenesis of ALS. Meanwhile, we also discussed the advantages, disadvantages, cost and availability of each models.
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Esclerose Lateral Amiotrófica , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Modelos Animais de Doenças , Neurônios Motores/metabolismo , Mutação/genética , Superóxido Dismutase/metabolismo , Camundongos TransgênicosRESUMO
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease that leads to the massive loss of motor neurons in cerebrum, brain stem and spinal cord. It affects not only motor neurons but also other neurons and glial cells, resulting in the progressive muscle atrophy, the severe disability and the eventual death due to the respiratory failure. The pathogenesis of ALS is not fully understood. Currently, several factors are considered to be involved in the pathogenesis of ALS, such as genetic factors, imbalances in protein homeostasis, RNA metabolism disorders, mitochondrial dysfunctions, glutamate-mediated excitatory toxicities and intra-neuronal material transport disorders in neurons. The study of genetic mutations related to ALS pathogenesis will link the molecular and cellular mechanisms of the disease, thus enhancing the understanding of its occurrence and progression, thereby providing new insights for the pathogenesis of ALS. This review summarizes the current insights in the molecular genetic pathogenesis of ALS.
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BACKGROUND: Hereditary spastic paraplegia 4 (SPG4) caused by spastin (SPAST) gene mutations accounts for 40-45% of hereditary spastic paraplegia (HSP) cases. To search for more genetic evidences for the pathogenesis of HSP, the SPAST genotype and clinical phenotype of a Chinese Han SPG4 family were analysed in this study. METHODS: The clinical data of the proband and his family members were collected. Whole genomic DNA was extracted from peripheral blood, and the gene detection and pathogenicity analysis of mutations were conducted using whole-exome sequencing technology. Suspected pathogenic mutations were identified. Verification within this family was conducted by Sanger sequencing. RESULTS: Eight (4 males and 4 females) of 20 members in 4 generations had SPG4. All patients presented with the high feet arches (pes cavus), the abnormal gait, the active tendon reflexes of the upper limbs, the hyperreflexia of the lower limbs, and the positive ankle clonus and Babinski's signs bilaterally. In the proband, we found a heterozygous mutation c.1495C > T in SPAST gene, which was associated with the autosomal dominant SPG4. Both the daughters and granddaughters of the proband in this family were verified to carry this mutation. The clinical characteristics of the SPG4 patients in this family are in line with the simple type of HSP. Heterozygous c.1495C > T is a pathogenic mutation in this family. CONCLUSION: In this study, we identified a c.1495C > T mutation in the SPAST gene in a Han Chinese family, enriching the mutation spectrum of SPG4.
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Paraplegia Espástica Hereditária , Humanos , Masculino , Feminino , Paraplegia Espástica Hereditária/diagnóstico , Espastina/genética , População do Leste Asiático , MutaçãoRESUMO
Current studies suggest that the abnormal alteration of brain lipid binding protein (BLBP) might participate in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, the detailed understanding of ALS pathogenesis been yet to be elucidated. Therefore, this research intended to explore the potential effects of BLBP in ALS. The observation and analysis of BLBP-altered features in various anatomical areas and different spinal segments was conducted at the pre-onset, onset, and progression stages of Tg(SOD1*G93A)1Gur (TG) mice and the same periods of age-matched SOD1 wild-type (WT) mice by fluorescence immunohistochemistry and western blotting. BLBP-positive cells were comprehensively distributed in various spinal anatomical areas, especially in both the anterior and posterior horn, around the central canal and in anterior, lateral, and posterior funiculi. Overall, BLBP expression tended to increase from the pre-onset to the onset to the progression stages of the same periods of age-matched WT mice. Furthermore, in TG mice, BLBP expression in the entire spinal cord significantly increased from onset to the progression stage. BLBP was expressed in neurons, astrocytes, and radial glial cells, and at the early and late stages of neural precursor cells (NPCs) and was predominantly distributed outside the cell nucleus. The increase of BLBP-positive cells was closely related to neural cell reduction in TG mice. The distribution and increased expression of BLBP among the cervical, thoracic, and lumbar segments of the spinal cord might participate in the development of ALS and exert potential effects in the pathogenesis of ALS by regulating NPCs.
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Esclerose Lateral Amiotrófica , Proteína 7 de Ligação a Ácidos Graxos , Células-Tronco Neurais , Animais , Camundongos , Esclerose Lateral Amiotrófica/genética , Proteína 7 de Ligação a Ácidos Graxos/genética , Superóxido Dismutase-1RESUMO
Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis (ALS) is closely linked to 5-hydroxytryptamine (5-HT). To investigate this further, we administered 5-HT receptor antagonists to SOD1*G93A transgenic (ALS mouse model) and wide-type mice. This involved intraperitoneal injections of either granisetron, piboserod, or ritanserin, which inhibit the 5-HT3, 5-HT4, and 5-HT2 receptors, respectively. The transgenic mice were found to have fewer 5-HT-positive cells in the spinal cord compared with wide-type mice. We found that the administration of granisetron reduced the body weight of the transgenic mice, while piboserod and ritanserin worsened the motor functioning, as assessed using a hanging wire test. However, none of the 5-HT receptor antagonists affected the disease progression. We analyzed the distribution and/or expression of TAR DNA binding protein 43 (TDP-43) and superoxide dismutase 1 G93A (SOD1-G93A), which form abnormal aggregates in ALS. We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists. In addition, the disease-related mislocalization of TDP-43 to the cytoplasm increased markedly for all three drugs. In certain anatomical regions, the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons. These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells. 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.
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BACKGROUND: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease in adults. However, ALS, especially sporadic ALS (sALS), is difficult to diagnose due to the lack of biomarkers. RESULTS: We used the bioinformatics technology to find the potential biomarker and we found that two hundred seventy-four DEGs were identified and enrichment analysis showed DEGs were involved in nervous system activity, like axon_guidance and the neurotrophin_signaling_pathway. Five nervous system-specific expressed hub genes were further validated by three GEO datasets. APP, LRRK2, and PSEN1 might be potential diagnostic and prognostic biomarkers of sALS, and NEAT1-miR-373-3p/miR-302c-3p/miR-372-3p-APP, circ_0000002-miR-302d-3p/miR-373-3p-APP and XIST-miR-9-5p/miR-30e-5p/miR-671-5p might be potential ceRNA regulatory pathways. APP SNP analysis showed subjects harboring the minor G allele of rs463946, minor G allele of rs466433 and minor C allele of rs364048 had an increased risk of sALS development. CONCLUSIONS: Our results identified three nervous system-specific expressed hub genes that might be diagnostic and prognostic markers of sALS and APP might be a genetic susceptibility factor contributing to sALS development.
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Esclerose Lateral Amiotrófica , MicroRNAs , Doenças Neurodegenerativas , Adulto , Humanos , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores , Biologia ComputacionalRESUMO
Heterogenous nuclear ribonucleoprotein G is down-regulated in the spinal cord of the Tg(SOD1*G93A)1Gur (TG) amyotrophic lateral sclerosis mouse model. However, most studies have only examined heterogenous nuclear ribonucleoprotein G expression in the amyotrophic lateral sclerosis model and heterogenous nuclear ribonucleoprotein G effects in amyotrophic lateral sclerosis pathogenesis such as in apoptosis are unknown. In this study, we studied the potential mechanism of heterogenous nuclear ribonucleoprotein G in neuronal death in the spinal cord of TG and wild-type mice and examined the mechanism by which heterogenous nuclear ribonucleoprotein G induces apoptosis. Heterogenous nuclear ribonucleoprotein G in spinal cord was analyzed using immunohistochemistry and western blotting, and cell proliferation and proteins (TAR DNA binding protein 43, superoxide dismutase 1, and Bax) were detected by the Cell Counting Kit-8 and western blot analysis in heterogenous nuclear ribonucleoprotein G siRNA-transfected PC12 cells. We analyzed heterogenous nuclear ribonucleoprotein G distribution in spinal cord in the amyotrophic lateral sclerosis model at various time points and the expressions of apoptosis and proliferation-related proteins. Heterogenous nuclear ribonucleoprotein G was mainly localized in neurons. Amyotrophic lateral sclerosis mice were examined at three stages: preonset (60-70 days), onset (90-100 days) and progression (120-130 days). The number of heterogenous nuclear ribonucleoprotein G-positive cells was significantly higher in the anterior horn of the lumbar spinal cord segment of TG mice at the preonset stage than that of control group but lower than that of the control group at the onset stage. The number of heterogenous nuclear ribonucleoprotein G-positive cells in both central canal and surrounding gray matter of the whole spinal cord of TG mice at the onset stage was significantly lower than that in the control group, whereas that of the lumbar spinal cord segment of TG mice was significantly higher than that in the control group at preonset stage and significantly lower than that in the control group at the progression stage. The numbers of heterogenous nuclear ribonucleoprotein G-positive cells in the posterior horn of cervical and thoracic segments of TG mice at preonset and progression stages were significantly lower than those in the control group. The expression of heterogenous nuclear ribonucleoprotein G in the cervical spinal cord segment of TG mice was significantly higher than that in the control group at the preonset stage but significantly lower at the progression stage. The expression of heterogenous nuclear ribonucleoprotein G in the thoracic spinal cord segment of TG mice was significantly increased at the preonset stage, significantly decreased at the onset stage, and significantly increased at the progression stage compared with the control group. heterogenous nuclear ribonucleoprotein G expression in the lumbar spinal cord segment of TG mice was significantly lower than that of the control group at the progression stage. After heterogenous nuclear ribonucleoprotein G gene silencing, PC12 cell survival was lower than that of control cells. Both TAR DNA binding protein 43 and Bax expressions were significantly increased in heterogenous nuclear ribonucleoprotein G-silenced cells compared with control cells. Our study suggests that abnormal distribution and expression of heterogenous nuclear ribonucleoprotein G might play a protective effect in amyotrophic lateral sclerosis development via preventing neuronal death by reducing abnormal TAR DNA binding protein 43 generation in the spinal cord.
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Background: The large-scale survey about amyotrophic lateral sclerosis (ALS) based on both population and hospitals in the Chinese mainland has been deficient at present. To this end, we conducted a cross-sectional survey about ALS based on the population and hospitals in seven provinces of the Chinese mainland in 2015-2016. Methods: We surveyed patients with ALS in seven provinces in eastern, middle, and western China. Among them, 13 prefecture-level cities, 13 municipal districts, 13 counties, 26 streets, 52 communities, 39 towns, and 78 administrative villages were selected for the population-based survey. Totally, 13 class-3 general hospitals, 13 class-2 general hospitals, and 26 street health centers or community health service centers in urban districts, and 13 county-level general hospitals, 39 township health centers, and 78 village clinics in rural districts were recruited for the hospital-based survey. Results: Among the Chinese mainland, the total prevalence of ALS was slightly lower than that of the world's other nations or districts. The male patients were more than female patients. The prevalence of rural residents was more than that of urban residents. The prevalence of farmers was higher than that of other professions. The majority of ALS was not accompanied by other chronic diseases. The peak onset age of ALS was higher, familial ALS (fALS) cases were slightly more, and the average survival duration of sporadic ALS (sALS) was slightly lower compared with the previous investigation data. The hospitalization expenses of almost 60% of ALS were not more than 10,000 Chinese Yuan. Conclusion: Hospitalization expenses in our survey objectives were the lowest in the current reported countries and districts. A farmer was a possible higher risk profession for ALS, the majority of ALS were not accompanied by other chronic diseases. Our survey provided more information on the epidemiology of ALS worldwide and supplied the deficiency of epidemiology survey about ALS from the Chinese mainland.