The relationship between pathological brain activity and functional network connectivity in glioma patients.

PURPOSE: Glioma is associated with pathologically high (peri)tumoral brain activity, which relates to faster progression. Functional connectivity is disturbed locally and throughout the entire brain, associating with symptomatology. We, therefore, investigated how local activity and network measures relate to better understand how the intricate relationship between the tumor and the rest of the brain may impact disease and symptom progression. METHODS: We obtained magnetoencephalography in 84 de novo glioma patients and 61 matched healthy controls. The offset of the power spectrum, a proxy of neuronal activity, was calculated for 210 cortical regions. We calculated patients' regional deviations in delta, theta and lower alpha network connectivity as compared to controls, using two network measures: clustering coefficient (local connectivity) and eigenvector centrality (integrative connectivity). We then tested group differences in activity and connectivity between (peri)tumoral, contralateral homologue regions, and the rest of the brain. We also correlated regional offset to connectivity. RESULTS: As expected, patients' (peri)tumoral activity was pathologically high, and patients showed higher clustering and lower centrality than controls. At the group-level, regionally high activity related to high clustering in controls and patients alike. However, within-patient analyses revealed negative associations between regional deviations in brain activity and clustering, such that pathologically high activity coincided with low network clustering, while regions with 'normal' activity levels showed high network clustering. CONCLUSION: Our results indicate that pathological activity and connectivity co-localize in a complex manner in glioma. This insight is relevant to our understanding of disease progression and cognitive symptomatology.

Post-translational modifications of Parkinson's disease-related proteins: Phosphorylation, SUMOylation and Ubiquitination.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the nigrostriatal pathway. The etiology of PD remains unclear and most cases are sporadic, however genetic mutations in more than 20 proteins have been shown to cause inherited forms of PD. Many of these proteins are linked to mitochondrial function, defects in which are a central characteristic of PD. Post-translational modifications (PTMs) allow rapid and reversible control over protein function. Largely focussing on mitochondrial dysfunction in PD, here we review findings on the PTMs phosphorylation, SUMOylation and ubiquitination that have been shown to affect PD-related proteins.

2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling.

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field.