Martínez Alonso, Emma

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Martínez Alonso, Emma

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Martínez Alonso, Emma

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Universidad de Murcia. Departamento de Biología Celular e Histología

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Open Access
Fragmentation of the Golgi complex of dopaminergic neurons in human substantia nigra: new cytopathological findings in Parkinson's disease
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Tomás, Mónica; Martínez Martínez, Narcisa; Cara Esteban, Mireia; Martínez Alonso, Emma; Martínez Menárguez, José Ángel
Fragmentation of the Golgi ribbon is a common feature of Parkinson's disease and other neurodegenerative diseases. This alteration could be the consequence of the anterograde and retrograde transport imbalance, α-synuclein aggregates, and/or cytoskeleton alterations. Most information on this process has been obtained from cellular and animal experimental models, and as such, there is little information available on human tissue. If the information on human tissue was available, it may help to understand the cytopathological mechanisms of this disease. In the present study, we analyzed the morphological characteristics of the Golgi complex of dopaminergic neurons in human samples of substantia nigra of control and Parkinson's disease patients. We measured the expression levels of putative molecules involved in Golgi fragmentation, including α-synuclein, tubulin, and Golgi-associated regulatory and structural proteins. We show that, as a consequence of the disease, the Golgi complex is fragmented into small stacks without vesiculation. We found that only a limited number of regulatory proteins are altered. Rab1, a small GTPase regulating endoplasmic reticulum-to-Golgi transport, is the most dramatically affected, being highly overexpressed in the surviving neurons. We found that the SNARE protein syntaxin 5 forms extracellular aggregates resembling the amyloid plaques characteristic of Alzheimer's disease. These findings may help to understand the cytopathology of Parkinson's disease.
Open Access
Volumetric modulated arc therapy for radiosurgery of brain metastases: a single-center study
(MDPI, 2023-09-07) Sánchez-Villalobos, José Manuel; Serna-Berna, Alfredo; Salinas-Ramos, Juan; Escolar-Pérez, Pedro Pablo; Andreu-Gálvez, Marina; Martínez Alonso, Emma; Pérez-Vicente, José Antonio; Alcaraz Baños, Miguel; Biología Celular e Histología; Facultad de Medicina
Whole-brain radiation therapy and stereotactic radiosurgery are two treatment modalities commonly utilized to treat brain metastases (BMs). The aim of this study is to retrospectively analyze the main radio-oncologic and clinical-demographic aspects of a cohort of BM patients treated with Volumetric Modulated Arc Therapy for radiosurgery (VMAT-RS). This is a cross-sectional observational design study with a retrospective review of the medical records of patients with brain metastases treated with VMAT-RS between 2012 and 2018. Clinical and demographic data, with special attention to sex, age, primary tumor, brain tumor-related epilepsy (BTRE), number and brain location of BMs, Karnofsky Performance Status (KPS), the updated DS-GPA prognostic index, and the survival estimated according to the Kaplan–Meier model from the date of radiosurgery, were analyzed. One hundred and twenty-one patients with 229 BMs were treated with VMAT-RS. Patients presented 1–4 BMs, which were treated with five non-coplanar VMAT arcs. Sixty-eight percent of the patients had lung cancer, and 35% of the BMs were in the frontal lobe. The proportion of local control was 88.5%. BTRE prevalence was 30.6%. The median survival time (MST) was 7.7 months. In the multivariate analysis of the Cox regression model, KPS ≥ 70 (HRKPS < 70 = 2.59; p = 0.001) and higher DS-GPA (HRDS-GPAII = 0.55, p = 0.022; HRDS-GPAIII-IV = 0.38, p = 0.006) were associated with improved survival. In the univariate analysis, primary tumor, age, and the presence of metastases in the posterior fossa (PFBMs) were also significant. In conclusion, the VMAT-RS is a technique with an overall survival rate comparable to other radiosurgery techniques. The median survival is significantly longer for those with higher KPS and DS-GPA. Other variables, such as the type of primary tumor, age, and PFBMs, could also influence survival, although further studies are needed.
Open Access
Low temperature (15ºC) induces COPII dissociation from membranes and slow exit from the endoplasmic reticulum in HeLa cells
(Springer, 2007-08-11) Tomás, Mónica; Ballesta Germán, José; Martínez Alonso, Emma; Martínez Menárguez, José Ángel; Biología Celular e Histología
Low temperature induces a transport blockade at the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) in cultured cells. Our previous studies support that the primary effect of low temperature is the detachment of COPI complexes from membranes. In the present study, we have used immunofluorescence and cryoimmunoelectron microscopy to investigate the effects of low temperature on both COPII and clathrin coat complexes in HeLa cells. Strikingly, COPII proteins moved from membranes to the cytosol at 15ºC, accumulating into electron-dense areas. In agreement with this observation, we also showed that ER exit is delayed in cells cultured at this temperature. By contrast, clathrin coat is not affected. Together, our results demonstrate that low temperature induces COPII dissociation from membranes and slow exit from the endoplasmic reticulum.
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Antiseizure medication for brain metastasis-related epilepsy: Findings of optimal choice from a retrospective cohort
(Elsevier, 2021-11-19) Sánchez-Villalobos, José Manuel; Aledo-Serrano, Ángel; Serna-Berna, Alfredo; Salinas-Ramos, Juan; Martínez Alonso, Emma; Pérez-Vicente, José Antonio; Alcaraz Baños, Miguel; Biología Celular e Histología; Facultad de Medicina
Objective: To analyze the prevalence of antiseizure medication (ASM) in patients with brain metastasis-related epilepsy (BMRE) treated with radiosurgery and the relationship between ASM and psychiatric comorbidity. Material and methods: This is a cross-sectional observational design study with retrospective review of medical records of all patients with brain metastases treated with volumetric modulated arc therapy radiosurgery (VMAT-RS) between 2012 and 2018 in a tertiary oncology center. We included those patients with BMRE, analyzing the clinical and demographic data, with special attention to psychiatric comorbidities and the use of ASM. Results: Of the 121 patients with brain metastases included for treatment with VMAT-RS, a total of 38 presented BMRE. The most widely used ASM as first-line treatment was levetiracetam (89%). Only 8% of the patients received sodium channel blockers. The most common psychiatric comorbidity was depression (42.1%). Conclusions: Levetiracetam is the most widely used ASM in patients with BMRE treated with VMAT-RS. Nevertheless, common psychiatric comorbidities in this population might change the decision-making of ASM choice.
Open Access
Structure and Dynamics of the Golgi Complex at 15ºC: Low Temperature Induces the Formation of Golgi-Derived Tubules
(Wiley, 2005-01) Egea, Gustavo; Ballesta Germán, José; Martínez Alonso, Emma; Martínez Menárguez, José Ángel; Biología Celular e Histología
Immunofluorescence and cryoimmunoelectron microscopy were used to examine the morphological and functional effects on the Golgi complex when protein transport is blocked at the ERGIC (ER-Golgi intermediate compartment) in HeLa cells incubated at low temperature (15ºC). At this temperature, the Golgi complex showed long tubules containing resident glycosylation enzymes but not matrix proteins. These Golgi-derived tubules also lacked anterograde (VSV-G) or retrograde (Shiga toxin) cargo. The formation of tubules was dependent on both energy and intact microtubule and actin cytoskeletons. Conversely, brefeldin A or cycloheximide treatments did not modify the appearance. When examined at the electron microscope, Golgi stacks were long and curved and appeared connected to tubules immunoreactive to galactosyltransferase antibodies but devoid of Golgi matrix proteins. Strikingly, COPI proteins moved from membranes to the cytosol at 15ºC which could explain the formation of tubules.
Open Access
Cytochemical and biochemical evidences for a complex tridimensional structure of the hamster zona pellucida
(Murcia : F. Hernández, 2009) Saavedra Leos, María Dolores; Gutiérrez Gallego, Ricardo; Fayrer Hosken, Richard; Ballesta Germán, José; Avilés Sánchez, Manuel; Castells Mora, María Teresa; Izquierdo Rico, María José; Jíménez Movilla, María; Martínez Alonso, Emma; Biología Celular
Zona pellucida (ZP) is an extracellular matrix that surrounds eggs and pre-implantation embryos and is required for in vivo fertility. A key event in successful fertilization is sperm binding to the surface of the ZP. It has been previously described that the hamster sperm binds mainly the outer region of the ZP which corresponds to the porous region in contact with the cumulus cells. Using ultrastructural cytochemistry approaches with an antibody developed against porcine ZP, this study shows that the pig ZP shares epitopes with some rodent species like hamster, rat and mouse. In the hamster, these epitopes are located mainly in the outer region of the ZP of preovulatory and ovulated oocytes. By means of biochemical approaches it was demonstrated that 1) the antibody is specific for the native hamster ZP3, 2) four different bands with a molecular weight of 67, 60, 48 and 38 kDa after Nlinked deglycosylation suggesting that the hamster ZP is formed by four proteins, and 3) the different composition observed in the outer region of the hamster ZP could be due to a specific supramolecular structure that makes some epitopes accessible for the antibodies. In summary, this study provides evidence that the different composition observed in the different regions of the ZP is mediated by a different organization of the components of the ZP produced during the oocyte maturation. This different organization could be responsible for the different sperm binding affinity observed for sperm to the outer region versus the inner region of the ZP.
Metadata only
Estructura, organización y dinámica del aparato de Golgi a 15ºC : papel de los túbulos en el transporte intra-Golgi / Emma Martínez Alonso; directores, José Angel Martínez Menárguez y José Ballesta Germán.
(Murcia : Universidad de Murcia, Departamento de Biología Celular,, 2006) Martínez Alonso, Emma
Open Access
The Golgi complex of dopaminergic enteric neurons is fragmented in a hemiparkinsonian rat model
(Wiley, 2023-10-19) Mireia Cara-Esteban; María Pilar Marín; Martínez Alonso, Emma; Sergio Martínez-Bellver; Vicent Teruel-Martí; Martínez Menárguez, José Ángel; Mónica Tomás; Biología Celular e Histología; Facultad de Medicina
Since gastrointestinal disorders are early consequences of Parkinson's disease (PD), this disease is clearly not restricted to the central nervous system (CNS), but also significantly affects the enteric nervous system (ENS). Large aggregates of the protein α-synuclein forming Lewy bodies, the prototypical cytopathological marker of this disease, have been observed in enteric nervous plexuses. However, their value in early prognosis is controversial. The Golgi complex (GC) of nigral neurons appears fragmented in Parkinson's disease, a characteristic common in most neurodegenerative diseases. In addition, the distribution and levels of regulatory proteins such as Rabs and SNAREs are altered, suggesting that PD is a membrane traffic-related pathology. Whether the GC of enteric dopaminergic neurons is affected by the disease has not yet been analyzed. In the present study, dopaminergic neurons in colon nervous plexuses behave as nigral neurons in a hemiparkinsonian rat model based on the injection of the toxin 6-OHDA. Their GCs are fragmented, and some regulatory proteins' distribution and expression levels are altered. The putative mechanisms of the transmission of the neurotoxin to the ENS are discussed. Our results support the possibility that GC structure and the level of some proteins, especially syntaxin 5, could be helpful as early indicators of the disease. Research Highlights: The Golgi complexes of enteric dopaminergic neurons appear fragmented in a Parkinson's disease rat model. Our results support the hypothesis that the Golgi complex structure and levels of Rab1 and syntaxin 5 could be helpful as early indicators of the disease.
Open Access
Focus on the Small GTPase Rab1: a key player in the pathogenesis of parkinson’s disease
(MDPI, 2021-11-08) Martínez Menárguez, José Ángel; Martínez Alonso, Emma; Cara-Esteban, Mireia; Tomás, Mónica; Biología Celular e Histología; Facultad de Medicina
Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. It is characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of large aggregates in the survival neurons called Lewy bodies, which mainly contain α-synuclein (α-syn). The cause of cell death is not known but could be due to mitochondrial dysfunction, protein homeostasis failure, and alterations in the secretory/endolysosomal/autophagic pathways. Survival nigral neurons overexpress the small GTPase Rab1. This protein is considered a housekeeping Rab that is necessary to support the secretory pathway, the maintenance of the Golgi complex structure, and the regulation of macroautophagy from yeast to humans. It is also involved in signaling, carcinogenesis, and infection for some pathogens. It has been shown that it is directly linked to the pathogenesis of PD and other neurodegenerative diseases. It has a protective effect against α–σψν toxicity and has recently been shown to be a substrate of LRRK2, which is the most common cause of familial PD and the risk of sporadic disease. In this review, we analyze the key aspects of Rab1 function in dopamine neurons and its implications in PD neurodegeneration/restauration. The results of the current and former research support the notion that this GTPase is a good candidate for therapeutic strategies. View Full-Text
Open Access
Safety and effectiveness of volumetric modulated arc therapy-based stereotactic radiosurgery for posterior fossa brain metastases: a single-centre experience
(MDPI, 2025-12-02) Sánchez-Villalobos, José Manuel ; Serna-Berna, Alfredo ; Salinas-Ramos, Juan ; Escolar-Pérez, Pedro Pablo ; Luengo-Gil, Ginés ; Andreu-Gálvez, Marina ; Martínez Alonso, Emma; Alcaraz Baños, Miguel; Biología Celular e Histología; Facultad de Medicina
Background/Objectives: Posterior fossa brain metastases (PFBMs) pose particular risks owing to their proximity to the brainstem and fourth ventricle. We evaluated the safety (treatment-related complications), local effectiveness, and procedural efficiency of volumetric modulated arc therapy (VMAT)-based stereotactic radiosurgery (VMAT-SRS) for PFBMs. Methods: This single-centre, retrospective study derived a PFBM subgroup from an overall institutional cohort of 123 patients treated with VMAT-RapidArc SRS/fSRS. The doses were 12–20 Gy (single fraction) or 5 × 6 Gy (selected cases). Local response (mRECIST) and predefined safety endpoints (symptomatic oedema with brainstem/IV-ventricle compromise, obstructive hydrocephalus, haemorrhagic transformation, CSF diversion, and urgent neurosurgery) were assessed. Overall survival and procedural time were analysed. Results: Thirty-one patients (39 lesions) were included; 76.9% of them received single-fraction SRS. In addition, 74.2% of patients had supratentorial metastases with posterior fossa involvement. Kaplan–Meier overall survival at 6, 12, 24, and 48 months was 74%, 58%, 26%, and 9.7%, respectively; the median survival time was 12.6 months. Among evaluable lesions, local control was 84.5% (per-lesion response: 15.5% PD, 28.1% SD, 34.4% PR, and 22.0% CR). No clinically significant posterior fossa local complications were observed. Three patients developed radiation-induced leukoencephalopathy after whole-brain radiotherapy (WBRT) and radiosurgery for synchronous supratentorial metastases. The median procedural time was 25.0 min (IQR 9.0) with one isocentre versus 52.5 min (IQR 9.75) with two. Conclusions: VMAT-SRS/fSRS for PFBMs achieved high local control, very low posterior fossa toxicity, and favourable procedural efficiency, supporting its use as a safe, rapid, frameless alternative to WBRT and other radiosurgical platforms such as Gamma Knife in appropriately selected patients.