DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex.

Background: Epigenome-wide association studies (EWAS) based on human brain samples allow a deep and direct understanding of epigenetic dysregulation in Alzheimer's disease (AD). However, strong variation of cell-type proportions across brain tissue samples represents a significant source of data noise. Here, we report the first EWAS based on sorted neuronal and non-neuronal (mostly glia) nuclei from postmortem human brain tissues.

An albumin-based tumor-targeted oxaliplatin prodrug with distinctly improved anticancer activity .

The design of targeted platinum(iv) prodrugs is a very promising approach to enhance the low selectivity of platinum(ii) drugs towards cancerous tissue in order to reduce the impact on healthy tissue and, consequently, the often severe side-effects. Herein, we report a set of mono-functionalized cis- and oxaliplatin-based platinum(iv) complexes bearing a maleimide moiety, which allows selective binding to serum albumin in the bloodstream. This leads not only to a prolonged plasma half-life by avoidance of fast renal clearance, but also to preferential accumulation of the drug in the tumor tissue due to the EPR-effect.

Targeting a Targeted Drug: An Approach Toward Hypoxia-Activatable Tyrosine Kinase Inhibitor Prodrugs.

Tyrosine kinase inhibitors (TKIs), which have revolutionized cancer therapy over the past 15 years, are limited in their clinical application due to serious side effects. Therefore, we converted two approved TKIs (sunitinib and erlotinib) into 2-nitroimidazole-based hypoxia-activatable prodrugs. Kinetics studies showed very different stabilities over 24 h; however, fast reductive activation via E.

Altered Long Noncoding RNA Expression Precedes the Course of Parkinson's Disease-a Preliminary Report.

Parkinson's disease (PD) is a slowly progressing neurodegenerative disorder that affects approximately seven million patients worldwide. Despite intensive research, the molecular mechanisms initiating and promoting PD are still unknown. However, it is assumed that environmental factors trigger PD.