Parkinson’s disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies (LB). During the course of disease, misfolded α-synuclein, the major constituent of LB, spreads to different regions of the brain in a prion-like fashion, giving rise to successive non-motor and motor symptoms. Etiology is likely multifactorial, and involves interplay among aging, genetic susceptibility and environmental factors. The prevalence of PD rises exponentially with age, and aging is associated with impairment of cellular pathways which increases susceptibility of dopaminergic neurons to cell death. However, the majority of those over the age of 80 do not have PD, thus other factors in addition to aging are needed to cause disease. Discovery of neurotoxins which can result in parkinsonism led to efforts in identifying environmental factors which may influence PD risk. Nevertheless, the causality of most environmental factors is not conclusively established, and alternative explanations such as reverse causality and recall bias cannot be excluded. The lack of geographic clusters and conjugal cases also go against environmental toxins as a major cause of PD. Rare mutations as well as common variants in genes such as SNCA, LRRK2 and GBA are associated with risk of PD, but Mendelian causes collectively only account for 5% of PD and common polymorphisms are associated with small increase in PD risk. Heritability of PD has been estimated to be around 30%. Thus, aging, genetics and environmental factors each alone is rarely sufficient to cause PD for most patients. PD is a multifactorial disorder involving interplay of aging, genetics and environmental factors. This has implications on the development of appropriate animal models of PD which take all these factors into account. Common converging pathways likely include mitochondrial dysfunction, impaired autophagy, oxidative stress and neuroinflammation, which are associated with the accumulation and spread of misfolded α-synuclein and neurodegeneration. Understanding the mechanisms involved in the initiation and progression of PD may lead to potential therapeutic targets to prevent PD or modify its course.

Glioma is the most common primary brain tumor and its prognosis is poor. Despite surgical removal, glioma is still prone to recurrence because it grows rapidly in the brain, is resistant to chemotherapy, and is highly aggressive. Therefore, there is an urgent need for a platform to study the cell dynamics of gliomas in order to discover the characteristics of the disease and develop more effective treatments. Although 2D cell models and animal models in previous studies have provided great help for our research, they also have many defects. Recently, scientific researchers have constructed a 3D structure called Organoids, which is similar to the structure of human tissues and organs. Organoids can perfectly compensate for the shortcomings of previous glioma models and are currently the most suitable research platform for glioma research. Therefore, we review the three methods currently used to establish glioma organoids. And introduced how they play a role in the diagnosis and treatment of glioma. Finally, we also summarized the current bottlenecks and difficulties encountered by glioma organoids, and the current efforts to solve these difficulties.

Synaptogyrin-3 (SYNGR3) is a synaptic vesicular membrane protein. Amongst four homologues (SYNGR1 to 4), SYNGR1 and 3 are especially abundant in the brain. SYNGR3 interacts with the dopamine transporter (DAT) to facilitate dopamine (DA) uptake and synaptic DA turnover in dopaminergic transmission. Perturbed SYNGR3 expression is observed in Parkinson’s disease (PD). The regulatory elements which affect SYNGR3 expression are unknown. Nuclear-receptor-related-1 protein (NURR1) can regulate dopaminergic neuronal differentiation and maintenance via binding to NGFI-B response elements (NBRE). We explored whether NURR1 can regulate SYNGR3 expression using an in silico analysis of the 5′-flanking region of the human SYNGR3 gene, reporter gene activity and an electrophoretic mobility shift assay (EMSA) of potential cis-acting sites. In silico analysis of two genomic DNA segments (1870 bp 5′-flanking region and 1870 + 159 bp of first exon) revealed one X Core Promoter Element 1 (XCPE1), two SP1, and three potential non-canonical NBRE response elements (ncNBRE) but no CAAT or TATA box. The longer segment exhibited gene promoter activity in luciferase reporter assays. Site-directed mutagenesis of XCPE1 decreased promoter activity in human neuroblastoma SH-SY5Y (↓43.2%) and human embryonic kidney HEK293 cells (↓39.7%). EMSA demonstrated NURR1 binding to these three ncNBRE. Site-directed mutagenesis of these ncNBRE reduced promoter activity by 11–17% in SH-SY5Y (neuronal) but not in HEK293 (non-neuronal) cells. C-DIM12 (Nurr1 activator) increased SYNGR3 protein expression in SH-SY5Y cells and its promoter activity using a real-time luciferase assay. As perturbed vesicular function is a feature of major neurodegenerative diseases, inducing SYNGR3 expression by NURR1 activators may be a potential therapeutic target to attenuate synaptic dysfunction in PD.

Vestigial dopaminergic cells in PD have selectivity for a sub-class of hypersensitive neurons with the nigrostriatal dopamine (DA) tract. DA is modulated in pre-synaptic nerve terminals to remain stable. To be specific, proteins at DA release sites that have a function of synthesizing and packing DA in cytoplasm, modulating release and reingestion, and changing excitability of neurons, display regional discrepancies that uncover relevancy of the observed sensitivity to neurodegenerative changes. Although the reasons of a majority of PD cases are still indistinct, heredity and environment are known to us to make significant influences. For decades, genetic analysis of PD patients with heredity in family have promoted our comprehension of pathogenesis to a great extent, which reveals correlative mechanisms including oxidative stress, abnormal protein homeostasis and mitochondrial dysfunction. In this review, we review the constitution of presynaptic vesicle related to DA homeostasis and describe the genetic and environmental evidence of presynaptic dysfunction that increase risky possibility of PD concerning intracellular vesicle transmission and their functional outcomes. We summarize alterations in synaptic vesicular proteins with great involvement in the reasons of some DA neurons highly vulnerable to neurodegenerative changes. We generalize different potential targets and therapeutic strategies for different pathogenic mechanisms, providing a reference for further studies of PD treatment in the future. But it remains to be further researched on this recently discovered and converging mechanism of vesicular dynamics and PD, which will provide a more profound comprehension and put up with new therapeutic tactics for PD patients.

Introduction: Congenital muscular dystrophy (CMD) is a group of early-onset disorders with clinical and genetic heterogeneity. Patients always present with muscle weakness typically from birth to early infancy, delay or arrest of gross motor development, and joint and/or spinal rigidity. There are various genes related to the development of CMD. Among them, mutations in integrin alpha 7 (ITGA7) is a rare subtype. The identification of disease-causing genes facilitates the diagnosis and treatment of CMD.Methods: We screened ITGA7 mutations in four people by whole exome sequencing and targeted sequencing from a consanguineous family. We then carried out electromyography and neuroelectrophysiological examinations to clarify a clinical picture of the patient diagnosed with CMD.Results: We report a Chinese boy diagnosed with CMD who carries a homozygous variant (c.1088dupG, p.H364Sfs^*15) of the ITGA7 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance.Conclusions: Our case further shows that ITGA7 mutation is related to CMD. Genetic counseling and multidisciplinary management of CMD play an important role in helping patients and their family. Further elucidation of the significant clinical and genetic heterogeneity, therapeutic targets, and the clinical care for patients remains our challenge for the future.

Circular RNAs (circRNAs) are novel noncoding RNAs that play regulatory roles in gene expression. Dysregulation of circRNAs is associated with the development and progression of several diseases, such as diabetes mellitus, nervous system diseases, cardiovascular diseases, and cancer. CircRNAs functionally participate in cell physiological activities through various molecular mechanisms. However, these molecular mechanisms are unclear. Oxidative stress is an essential factor in the pathogenesis of various diseases, including neurological diseases. Emerging roles of circRNAs have been identified in different systems in response to oxidative stress. In this review, we summarize the current understanding of circRNA biogenesis, properties, expression profiles, and the clues indicating the regulatory roles of circRNAs through oxidative stress in various systems, especially the nervous system.