Human genetics and neuropathology suggest a link between miR-218 and amyotrophic lateral sclerosis pathophysiology

Motor neuron–specific microRNA-218 (miR-218) has recently received attention because of its roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons. However, in amyotrophic lateral sclerosis (ALS) motor neurons, miR-218 is down-regulated and its mRNA targets are reciprocally up-regulated (derepressed). We further identify the potassium channel Kv10.1 as a new miR-218 direct target that controls neuronal activity. In addition, we screened thousands of ALS genomes and identified six rare variants in the human miR-218-2 sequence. miR-218 gene variants fail to regulate neuron activity, suggesting the importance of this small endogenous RNA for neuronal robustness. The underlying mechanisms involve inhibition of miR-218 biogenesis and reduced processing by DICER. Therefore, miR-218 activity in motor neurons may be susceptible to failure in human ALS, suggesting that miR-218 may be a potential therapeutic target in motor neuron disease

Institutional Governance of European Neighbourhood Policy in the Wake of the Arab Spring

This paper analyses the goals and instruments of the European Neighbourhood Policy (ENP) before and after the Arab Spring, and enquires why there has been little substantive change in the European Union's (EU's) approach to the neighbourhood, notwithstanding the acknowledged opportunity for democratic change and the EU's stated willingness to contribute to it. It argues that the institutional governance of the ENP has largely conditioned the EU's response to the historic changes in the neighbourhood. The EU's actorness has been tamed by the underlying differences among EU member states and this has particularly played out in policy areas where the EU institutions have less freedom to act on behalf of the Union. Overall, the EU has asserted itself as neither a strategic actor nor a normative power, but rather as a bystander, trapped in its internal institutional process and passively reacting to crisis events by proposing long-term solutions with little short-term impact