Nova Reader - Subject

A New Approach to the Development of Disease‐Modifying Therapies for PD; Fighting Another Pandemic

2020-10-07T00:00

A disease‐modifying therapy that slows disease progression and development of disability is the major unmet need in the treatment of Parkinson's disease. Recent scientific advances suggest many promising and exciting new interventions. However, despite these opportunities, the cost, time and uncertainty of being able to receive an indication as a disease‐modifying therapy has caused many pharmaceutical companies to abandon development of potentially disease‐modifying drugs. We propose a new approach to development of these agents that will reduce the cost and facilitate approval of putative disease‐modifying drugs that should prove acceptable to pharmaceutical companies and regulatory agencies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Stress and Mindfulness in Parkinson's Disease: Clinical Effects and Potential Underlying Mechanisms

2020-10-23T00:00

Patients with Parkinson's disease (PD) are very vulnerable to the negative effects of psychological distress: neuropsychiatric symptoms, such as anxiety and depression, are highly prevalent in PD; motor symptoms (such as tremor) typically worsen in stressful situations; and dopaminergic medication is less effective. Furthermore, animal studies of PD suggest that chronic stress may accelerate disease progression. Adequate self‐management strategies are therefore essential to reduce the detrimental effects of chronic stress on PD. Mindfulness‐based interventions encourage individuals to independently self‐manage and adapt to the challenges created by their condition. In PD, emerging clinical evidence suggests that mindfulness‐based interventions may reduce psychological distress and improve clinical symptoms, but insight into the underlying mechanisms is lacking. In this viewpoint, we provide a systematic overview of existing mindfulness trials in PD. Furthermore, we discuss the cerebral mechanisms involved in acute and chronic stress, and the impact of mindfulness‐based interventions on these networks. In addition, we delineate a hypothetical mechanistic framework of how chronic stress may increase the susceptibility for neuropsychiatric symptoms in PD and may potentially even influence disease progression. We end with offering recommendations for future research. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Rashomon at the kinetochore: Function(s) of the Mad1–cyclin B1 complex

2020-07-02T00:00

Houston et al. synthesize recent work analyzing Mad1–cyclin B1 complex function in mitosis.

In the film Rashomon, four witnesses describe seemingly contradictory views of one event. In a recent analogy, an interaction between the master mitotic regulator cyclin B1 and the spindle checkpoint component Mad1 was independently described by three groups who propose strikingly different functions for this interaction. Here, we summarize their findings and present a perspective on reconciling the different views.

Confounding factors from inducible systems for spatiotemporal gene expression regulation

2020-05-19T00:00

This Reproducibility Viewpoint discusses confounding factors of Tet-On/Tet-Off and Cre/loxP systems, including doxycycline-induced microbiome alterations, mitochondrial dysfunction, and tamoxifen-induced toxicity.

Spatiotemporally regulated targeted gene manipulation is a common way to study the effect of gene variants on phenotypic traits, but the Cre/loxP and Tet-On/Tet-Off systems can affect whole-organism physiology and function due to off-target effects. We highlight some of these adverse effects, including whole-body endocrinology and disturbances in the gut microbiome and in mitochondrial and metabolic function.