A novel variant of PLA2G6 gene related early-onset parkinsonism: a case report and literature review.

This study reported a case of early-onset parkinsonism associated with a novel variant of the PLA2G6 gene. The boy first started showing symptoms at the age of 11, with gait instability and frequent falls. As the disease progressed, his gait instability worsened, and he developed difficulties with swallowing and speaking, although there was no apparent decline in cognitive function. An MRI of the head revealed significant atrophy of the cerebellum. The initial diagnosis for the boy was early-onset parkinsonism, classified as Hoehn-Yahr grade 5.Genomic sequencing of the patient indicated that he had compound heterozygous variations in the PLA2G6 gene: c.1454G>A (p.Gly485Glu) and c.991G>T (p.Asp331Tyr). Pedigree analysis revealed that his younger brother also carried the same variant, albeit with milder symptoms. The patient's unaffected mother was found to be a carrier of the c.991G>T variant. Additionally, this study reviewed 62 unrelated families with PLA2G6 gene-related early-onset parkinsonism. The analysis showed a higher proportion of female probands, with a mean age of onset of ~23.0 years. Primary symptoms were predominantly bradykinesia and psychosis, with tremors being relatively rare. Cerebellar atrophy was observed in 41 patients (66.1%). Among the reported mutations, the most common mutation was c.991G>T, presenting in 21 families (33.9%), followed by c.2222G>A in eight families (12.9%). Other mutations were less common. Notably, the c.991G>T mutation was exclusive to Chinese families and was a prevalent mutation among this population. The initial symptoms varied significantly among patients with different mutations.

Efficacy and safety of intravenous thrombolysis with alteplase for treating acute ischemic stroke at different time windows: A protocol for systematic review and meta-analysis.

BACKGROUND: As the priority drug for treating acute ischemic stroke (AIS), alteplase is a thrombolytic drug with strong fibrin specificity. It can obviously treat AIS with high safety. However, the validity of its time window is controversial. This study focus on the efficacy and safety of intravenous thrombolysis with alteplase for treating AIS at different time windows. METHODS: Retrieval of English database (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese database was conducted (China National Knowledge Infrastructure, WAN FANG, VIP, China Biology Medicine disc) by computers. From the establishment of the database to October 2020, a retrospective study and case-control study on intravenous thrombolysis at different time windows for treating AIS were conducted. Two researchers independently conducted data extraction and quality evaluation of literature on the included studies, and RevMan5.3 was used for Meta-analysis on the included literature. RESULTS: This study aims to evaluate the efficacy and safety of intravenous thrombolysis with alteplase at different time windows for treating AIS by National Institutes of Health Stroke Scale score, modified Rankin Scale rating scale, spontaneous intracerebral hemorrhage incidence rate, All-cause mortality, and so on. CONCLUSIONS: This study will provide an evidence-based basis for the clinical efficacy of alteplase for treating AIS by thrombolytic therapy at different time windows. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605 / OSF.IO / K7PHB.

Effects of miR-199a on autophagy by targeting glycogen synthase kinase 3ß to activate PTEN/AKT/mTOR signaling in an MPP+ in vitro model of Parkinson's disease.

Objectives: miR-199a can regulate autophagy, its underlying mechanisms remain unknown. The purpose of this study was to investigate the mechanisms of miR-199a involved in regulating autophagy in a 1-methyl-4-phenylpyridine (MPP+)-induced in vitro model of PD.Methods: PC12 cells were incubated in MPP+, and the expression levels of miR-199a were bidirectionally regulated via either transfection of an miR-199a mimic or incubation in miR-199a inhibitors. The experimental manipulations were divided into four groups, including the control group, MPP+ group, MPP+ + miR-199a mimic group, and MPP+ + miR-199a inhibitor group. MTT, CCK-8, qRT-PCR, Western blotting and linear correlation analysis were performed to evaluate various experimental indicators.Results: At increasing MPP+ concentrations, the following results were found: the expression levels of miR-199a, phosphorylated AKT and mTOR proteins expression decreased; the expression levels of phosphatase and tensin homologue (PTEN), GSK3ß, Beclin1, and LC3II increased; PC12 autophagy increased; and cellular viability and survival rates decreased. Transfection of an miR-199a mimic increased miR-199a expression and induced all of the following: the expression levels of PTEN, GSK3ß, Beclin1, and LC3II decreased; the expression levels of phosphorylated AKT and mTOR proteins expression increased; PC12 autophagy decreased; and cellular viability and survival rates increased.Discussion: In this in vitro study, we found that increasing miR-199a expression in PC12 cells reduced protein levels of Beclin1 and LC3II, decreased autophagy, enhanced cellular viability, increased survival rate, and ameliorated MPP+-induced parkinsonian-like cellular pathologies by targeting pro-autophagic pathways and GSK3ß to activate PTEN/AKT/mTOR signaling.