Reviews & Analysis

Psychiatric disorders are difficult to model owing to their inherent complexity and heterogeneity. This Perspective focuses on the use of 3D brain organoids in modeling these disorders, considering both their advantages and their limitations.

Recent evidence indicates that one of the underlying mechanisms in the pathogenesis of neuropsychiatric disorders is dysregulated dentate gyrus neurogenesis. Here the authors present evidence supporting this hypothesis and suggest therapeutic avenues.

Abi-Dargham and Horga discuss the challenges of developing and standardizing brain-imaging technologies to aid with the diagnosis and treatment of psychiatric disorders.

The International AIDS Society Towards a Cure Working Group lays out its scientific strategy to achieve a cure for HIV.

Ron Duman and colleagues discuss recent insights into a role for circuit disruption in the mechanisms of stress-induced depression. Furthermore they discuss the potential for rapid-acting antidepressants to alleviate these defects.

Prospects for engineered T cell therapy of solid tumors.

In this Perspective, the mechanisms by which proteostasis is coordinated within and between cells is discussed with an emphasis on how these mechanisms are deregulated upon aging.

In this Perspective, the current approaches to drug aging, and how new approaches may be developed in the future are discussed.

In this Perspective, the authors discuss the currently available models for psychiatric disease modeling. They present a framework for translating new knowledge by placing more emphasis on identifying neurophysiological defects.

In this Perspective, attendees of the Herrenhausen Tumour Heterogeneity meeting discuss the challenges in understanding tumour heterogeneity and propose ways forward for overcoming these hurdles.

In this Perspective, the authors discuss the importance of intrinsic and extrinsic factors in muscle regeneration, and they conclude that both are necessary for the action of muscle stem cells in the aging process.

In this Perspective, Fred De Sauvage and Stephen Gould discuss the suitability of different mouse models for modeling cancer pathogenic processes, with an emphasis on applicability to developing cancer therapies.

Understanding the regenerative capacity of the adult mammalian heart and the cell types involved is essential for developing therapies for cardiac repair.

Our understanding of stem cell biology is increasing, but the translation of this knowledge into regenerative medicine therapies for aged or diseased tissues is proving challenging. In this Perspective, four experts in the field discuss strategies for overcoming the major hurdles facing the translational regenerative field.

Synthetic lethality describes a situation in which defects in either one of two genes are not detrimental, but combining defects in the two genes is lethal. The targeting of BRCA-deficient tumors by PARP inhibitors is the first clinical example utilizing the principle of synthetic lethality to treat cancer. Despite the promise of this approach, a number of resistance mechanisms have been identified, and this Perspective describes these mechanisms and their clinical relevance.

There is much interest in the applications of pluripotent stem cells for regenerative medicine. In this Perspective, the authors discuss the factors that might contribute to the potential risk of tumorigenicity from pluripotent stem cell therapies. They also outline recent developments in techniques that allow the sorting of tumorigenic species from nontumorigenic cells and offer a viewpoint into the future hurdles for moving pluripotent stem cell–based therapies from bench to bedside.

Persistence of hepatitis C virus contributes to chronic infection, which can lead to liver fibrosis and even liver cancer. Different factors, such as host genetics and immunity and viral immune evasion strategies, account for the outcome of the infection and the patient response to antivirals. This Perspective discusses how the interaction of these factors modulates viral immunity and how they might be used to identify the key targets to mount an effective immune response that will clear the virus and improve drug response.

Autism spectrum disorders (ASDs) are a clinically heterogeneous group of neurodevelopmental disorders characterized by social and communication deficits and repetitive behaviors. In a subset of individuals with ASD, mutations in genes involved in synaptic function have been identified, and this Perspective discusses the evidence from mouse models of ASD that synaptic deficits can be ameliorated in the mature brain. The authors also suggest a strategy for designing more informative clinical trials for ASD therapies that stratify patients according to their specific synaptic mutations.