RESUMEN
Background: Parkinson's disease (PD) is marked by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and cognitive dysfunctions. The molecular mechanisms underlying synaptic alterations in PD remain elusive, with a focus on the role of Itga5 in synaptic integrity and motor coordination and TAT-Itga5 was designed to suppress PTEN activity in this investigation. Methods: This study utilized MPTP-induced PD animal models to investigate the expression and role of Itga5 in the striatum. Techniques included quantitative PCR, Western blotting, immunostaining, CRISPR-CasRx-mediated knockdown, electrophysiological assays, behavioral tests, and mass spectrometry. Results: Itga5 expression was significantly reduced in MPTP-induced PD models. In these models, a marked decrease in dendritic spine density and a shift towards thinner spines in striatal GABA neurons were observed, suggesting impaired synaptic integration. Knockdown of Itga5 resulted in reduced dendritic branching, decreased mushroom spines, and increased thin spines, altering synaptic architecture. Electrophysiological analyses revealed changes in action potential and spontaneous excitatory postsynaptic currents, indicating altered synaptic transmission. Motor behavior assessments showed that Itga5 deficiency led to impairments in fine motor control and coordination. Furthermore, Itga5 was found to interact with PTEN, affecting AKT signaling crucial for synaptic development and motor coordination. Conclusion: The study demonstrates that Itga5 plays a critical role in maintaining synaptic integrity and motor coordination in PD. The Itga5-PTEN-AKT pathway represents a potential therapeutic target for addressing synaptic and motor dysfunctions in PD.
Asunto(s)
Fosfohidrolasa PTEN , Enfermedad de Parkinson , Transducción de Señal , Animales , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/genética , Masculino , Ratones , Cuerpo Estriado/metabolismo , Ratones Endogámicos C57BL , Integrina alfa5/metabolismo , Integrina alfa5/genética , Sinapsis/metabolismo , Modelos Animales de EnfermedadRESUMEN
BACKGROUND AND PURPOSE: The aim of this study was to discover the associations between HMOX-1 and Alzheimer's disease (AD). METHODS: A total of 500 AD patients and 500 healthy controls were recruited in this study. Polymer chain reaction was used. RESULTS: There was a statistically significant difference between AD patients and controls in both the dominant and recessive models of HMOX-1 rs2071746 after adjustment for age, gender and education (dominant model: p = 0.047, odds ratio [OR] 1.34, 95% confidence interval [CI] 1.00-1.78, adjusted; recessive model: p = 0.049, OR 1.34, 95% CI 1.00-1.80, adjusted). There was also a trend for an association between the dominant model and late-onset AD after adjustment for age, gender and education (dominant model: p = 0.084, OR 1.37, 95% CI 0.96-1.95, adjusted). CONCLUSIONS: We found an association between the dominant and recessive models of HMOX1 rs2071746 and AD.
Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
STUDY OBJECTIVES: The aim was to investigate whether fatigue could predict the development of motor symptoms of Parkinson's disease (PD) in a southern Chinese population. METHODS: In total, 246 PD patients were recruited. All patients were evaluated by Fatigue Severity Scale (FSS), Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and Unified PD Rating Scale provided by Movement Disorders Society (MDS-UPDRS). MDS-UPDRS was re-evaluated after 2 years. RESULTS: FSS scores were associated with total score and subparts of MDS-UPDRS (total: p 0.039, p 0.030, adjusted; part III: p 0.022, p 0.016, adjusted). CONCLUSIONS: The symptom of subjective fatigue could predict the progression of PD.
Asunto(s)
Progresión de la Enfermedad , Fatiga/diagnóstico , Fatiga/epidemiología , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/epidemiología , Anciano , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The recent publication of the complete sequence of human chromosome 6 provides a platform from which to investigate genomic sequence variation. We report here a detailed linkage disequilibrium (LD) pattern map across the entire human chromosome 6p by using a set of 1152 single nucleotide polymorphisms (SNPs) in a population of 198 Singaporean Chinese, with 326 SNPs focused in the major histocompatibility complex (MHC) region. Our analysis shows some unexpectedly high segments of strong LD in a 10-Mb region that includes the extremely polymorphic and gene-rich MHC loci and many non-MHC genes. These include the telomeric peri-MHC region that harbors olfactory receptors, histones and zinc finger clusters, and the centromeric peri-MHC region that contains several unknown open reading frames. The data also help refine a human-mouse synteny break in the region between 28.6 and 29.4 Mb. The population-based LD map presented here will provide an essential resource for understanding the genomic sequence variation of chromosome 6p and LD mapping of disease genes of complex genetic traits.