Review Articles in 2016

The biological rationale for targeting protein–protein interactions as a therapeutic strategy is strong, but identifying viable small-molecule drugs to achieve this has proved highly challenging. This article uses examples of successful discovery efforts to illustrate the research strategies that have proved most useful for different classes of protein–protein interactions.

Anti-inflammatory treatments reduce inflammation but do not necessarily encourage resolution. Here, Fullerton and Gilroy suggest that some chronic inflammatory disorders may be characterized by an inability to resolve inflammation, and discuss the biology of resolution and translational efforts to target it.

Insulin continues to represent a cornerstone therapy for diabetes, but its use is limited by its narrow therapeutic index. Here, DiMarchi and colleagues provide an overview of the history of the development and use of insulin as an antidiabetic agent, focusing on recent approaches to improve the efficacy, safety and convenience of insulin therapy.

Current therapies for obesity have limited efficacy and may be associated with substantial adverse effects. Cinti and colleagues discuss the conversion of white fat to brown, thermogenic fat as a potential strategy to curb obesity. Adipocyte conversion could be particularly important in the visceral compartment, as fat in this region is associated with morbidity but is also particularly prone to transdifferentiation.

Metabolomics is rapidly emerging as an important tool in understanding disease mechanisms and identifying novel therapeutic strategies. Here, Wishart explores recent developments in metabolomics technologies, focusing on the growing role of metabolomics in drug discovery and its potential effect on precision medicine.

Advances in the understanding of the genetic and environmental causes of schizophrenia, and their relationship to aberrant patterns of neurodevelopment, have led to growing interest in the possibility that 'disease-modifying' strategies could alter the course to — and of — this debilitating disorder, rather than just alleviating its symptoms. This article provides a broad-based consideration of the challenges and opportunities inherent in such efforts.

Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which are caused by coronaviruses, have attracted substantial attention owing to their high mortality rates and potential to cause epidemics. Yuen and colleagues discuss progress with treatment options for these syndromes, including virus- and host-targeted drugs, and the challenges that need to be overcome in their further development.

Research on the blood–brain barrier (BBB) has led to the concept of a complex, dynamic interface between the central nervous system (CNS) and periphery. Banks considers how this new understanding can combine with classical concepts to inform CNS drug delivery strategies and promote BBB integrity in various diseases.

Non-alcoholic steatohepatitis (NASH) is increasing in prevalence, partially because of the pervasiveness of obesity. In this Review, Musso and colleagues discuss potential future approaches to treat this disease, including those that target causes, such as inflammation and aberrant metabolism, as well as those that target fibrosis, one of the key features of patients with NASH.

Forms of cell death besides apoptosis and necrosis are becoming increasingly well understood, and are relevant to many disease contexts. Here, Conradet al. describe the mechanisms underlying regulated forms of necrosis — including necroptosis, ferroptosis, parthanatos and cyclophilin D-mediated necrosis — and efforts to induce or prevent them in disease.