In most mammalian cells, the Golgi complex forms a continuous ribbon. In neurodegenerative diseases, the Golgi ribbon of a specific group of neurons is typically broken into isolated elements, a very early event which happens before clinical and other pathological symptoms become evident. It is not known whether this phenomenon is caused by mechanisms associated with cell death or if, conversely, it triggers apoptosis. When the phenomenon was studied in diseases such as Parkinson’s and Alzheimer’s or amyotrophic lateral sclerosis, it was attributed to a variety of causes, including the presence of cytoplasmatic protein aggregates, malfunctioning of intracellular traffic and/or alterations in the cytoskeleton. In the present review, we summarize the current findings related to these and other neurodegenerative diseases and try to search for clues on putative common causes.

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.

Background: Whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are two treatment modalities commonly utilized to treat brain metastases (BMs). Aim: The purpose of this study is to analyze retrospectively the local control and survival of patients with BMs of breast cancer (BC) treated via radiosurgery using Volumetric Modulated Arc Therapy (VMAT-RS). Methods: 18 patients with 41 BMs of BC and treated by VMAT-RS were studied. They were classified according to the molecular subtype of BC and the modified breast graded prognostic assessment -GPA- index. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. The spatial distribution of BMs, the influence of receptor status on the location of the lesions and survival assessed via the Kaplan-Meier model were analyzed. Results: The median survival time (MST) was 19.7 months. Statistically significant differences were determined in the MST according to the Karnofsky performance status (p= 0.02) and the HER2 status (p= 0.004), being more prolonged in the HER2+ patients. Finally, our results showed that the cerebellum is the predominant site of breast cancer BMs, and also suggested that HER2+BMs had a predilection for some structures of the posterior circulation, such as the cerebellum, brainstem and occipital lobes (p= 0.048). Conclusions: The VMAT-RS is a technique with an overall survival compared to other radiosurgery techniques. The baseline situation at the time of treatment, the modified breast-GPA and the molecular subtypes are factors that significantly influence patient survival.

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 (HR_{KPS < 70} = 2.59; p = 0.001) and higher DS-GPA (HR_DS-GPAII = 0.55, p = 0.022; HR_DS-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.

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 retrospective review of 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 5 non-coplanar VMAT arcs. Sixty-eight percent of the patients had lung cancer and 35% of the BMs were in the frontal lobe. 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 KPS70 (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 significative. In conclusion, the VMAT-RS is a technique with an overall survival comparable to other radiosurgery techniques. The median survival is significantly longer in 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.

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.