ABSTRACT
OBJECTIVE: To explore the clinical manifestations and imaging features of neurosyphilis and to discuss the obstacles in the diagnosis and treatment of neurosyphilis. METHODS: We present this case study involving three cases of definite neurosyphilis, focusing on their clinical data. RESULTS: Case 1 is a patient with numb and weak left lower limb. Case 2 showed slow reaction and dementia behaviors including worse memory and the decrease of calculation and orientation ability in this patient. Case 3 is a peripheral incomplete left oculomotor nerve palsy patient. Magnetic resonance imaging findings of three patients are different. And single photon emission computed tomography showed the regional cerebral blood flow was all hypoperfused. There were some difficulties in diagnosing and treating the patients in these three cases. CONCLUSION: The clinical manifestations and imaging findings of neurosyphilis are diverse. Clinicians should pay attention to neurosyphilis. After clear diagnosis, patients would receive norm treatment in time.
Subject(s)
Magnetic Resonance Imaging/methods , Neurosyphilis/diagnosis , Neurosyphilis/therapy , Tomography, Emission-Computed, Single-Photon , Agglutination Tests , Antibodies, Bacterial/metabolism , Cerebrovascular Circulation , Cysteine/analogs & derivatives , Cysteine/pharmacokinetics , Diagnosis, Differential , Humans , Male , Mental Status Schedule , Middle Aged , Neurosyphilis/microbiology , Neurosyphilis/physiopathology , Organotechnetium Compounds/pharmacokinetics , Treponema pallidum/immunology , Treponema pallidum/pathogenicityABSTRACT
INTRODUCTION AND AIMS: The ASK1-JNK3 signaling pathway plays a pivotal role in the pathogenesis of Parkinson's disease (PD). The specific binding of ß-arrestin2 to JNK3 is essential for activation of the ASK1-JNK3 cascade, representing a potential therapeutic target for preventing dopaminergic neuronal death in PD. The aim of this study was to identify a novel strategy for the prevention of dopaminergic neuronal death in PD. METHODS: Based on the specific binding of ß-arrestin2 to JNK3, a 21-amino-acid fusion peptide, termed JNK3-N-Tat, was synthesized. We evaluated the ability of this peptide to inhibit the binding of ß-arrestin2 to its target domain in JNK3 in vitro and in vivo. RESULTS: The JNK3-N-Tat peptide inhibited activation of the ASK1-JNK3 cascade by disrupting the interaction between ß-arrestin2 and JNK3. JNK3-N-Tat exerted beneficial effects through pathways downstream of JNK3 and improved mitochondrial function, resulting in attenuated MPP+/MPTP-induced damage. JNK3-N-Tat protected mesencephalic dopaminergic neurons against MPTP-induced toxicity. CONCLUSIONS: JNK3-N-Tat, a JNK3-inhibitory peptide, protects dopaminergic neurons against MPP+/MPTP-induced injury by inhibiting the ASK1-JNK3 signaling pathway.
Subject(s)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects , Dopaminergic Neurons/cytology , Dopaminergic Neurons/drug effects , MAP Kinase Kinase Kinase 5/metabolism , Mitogen-Activated Protein Kinase 10/metabolism , Peptides/pharmacology , Signal Transduction/drug effects , Amino Acid Sequence , Animals , Apoptosis/drug effects , Arrestins/chemistry , Arrestins/metabolism , Cell Line, Tumor , Cytoprotection/drug effects , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathology , Humans , Male , Mice , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/pathology , Mitogen-Activated Protein Kinase 10/chemistry , Molecular Sequence Data , Parkinson Disease/pathology , Peptides/chemistry , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Structure, Tertiary , beta-ArrestinsABSTRACT
BACKGROUND: Recent studies highlight the role of DNA methylation in the pathogenesis of Parkinson's disease (PD). However, there is a paucity of studies exploring the role of blood-based DNA methylation in PD. We aimed to explore identifiable epigenetic biomarkers for PD by analyzing the methylation status of α-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2) in leukocytes. METHODS: Bisulfite Specific PCR-based Sequencing method was used for semi-quantitative detection of methylation status of CpG islands in SNCA and LRRK2 promoter regions. Bisulfite Specific Cloning-based Sequencing method was used for further quantitative examination of CpG-2 methylation of SNCA. mRNA level was also detected in leukocytes. RESULTS: Semi-quantitative detection showed that the methylation status of SNCA CpG-2 differed between PD patients and normal controls, while there was no difference in CpG-1 of SNCA or in LRRK2 promoter. Further quantitative analysis by clonal assay showed that the CpG-2 of SNCA was hypomethylated in PD patients compared with the normal control (5.90% versus 7.69%, P=0.034). Moreover, among the 14 CpG sites of CpG-2, the 2nd, 4th and 9th CpG sites were significantly hypomethylated in PD patients. In subgroups of PD, the methylation level decreased in the early-onset PD patients (P=0.001). RT-PCR examination showed that SNCA mRNA was increased in PD patients compared with normal control (P=0.003). CONCLUSIONS: Our results indicated that the methylation level of SNCA CpG-2, especially that of the 2nd, 4th and 9th CpG sites in leukocytes might have great potential to be a useful and informative biomarker in PD diagnosis and treatment.
