Volume 11 Issue 1, January 2015

The notion that the classic motor features of Parkinson disease (PD) are preceded by a prodrome has received renewed interest in the past decade. A recent study corroborates previous findings that smell loss and constipation are signifiers of nigral degeneration. But can we really predict who is going to get PD?

The recent TOPIC trial found that teriflunomide could prevent relapses in patients with clinically isolated syndrome (CIS). Many other multiple sclerosis (MS) therapies are effective for CIS, because CIS is the first clinical manifestation of MS for most patients. Questions remain over the utility of future trials like TOPIC.

LDL-lowering drugs are widely recommended for the secondary prevention of vascular events in patients who have experienced a stroke or transient ischaemic attack. As a new study illustrates, however, lipid management among this group remains inadequate, possibly placing patients at unnecessary risk of stroke recurrence.

After decades of near neglect, the importance of exercise for patients with Parkinson disease is being increasingly supported by recent studies in experimental animal models and controlled clinical trials. Now, an inverse relationship between physical activity and disease burden has been demonstrated in a large cohort study.

The network between mitochondia is in a constant state of flux, with organelles fusing and separating in response to cellular metabolic demands. Disturbances to mitochondrial fusion and fission have been observed in several human diseases, and in this Review, Florence Burté and colleagues discuss how the mitochondrial network might play a crucial part in neurodegeneration. The authors focus on major protein mediators of mitochondrial dynamics, including optic atrophy protein and the mitofusins, and trace the involvement of mitochondrial dynamics in autosomal dominant optic atrophy, Charcot–Marie–Tooth disease and other disorders.

Despite the promise that many potential neuroprotective treatments for Parkinson disease (PD) have shown in preclinical studies, the benefits have not been replicated in recent clinical trials. In this Review, Athauda and Foltynie discuss the reasons for this 'failure to translate', and propose strategies to avoid such eventualities in the future, including improved trial design and repositioning of existing drugs. They also review the most promising drugs that are currently in preclinical development or clinical testing for their neuroprotective properties in PD.

Despite a growing emphasis on biomarkers in research into Alzheimer disease (AD) and Parkinson disease (PD), there is little consensus as to which biomarkers are most effective. In this Review, Lleó and colleagues discuss cerebrospinal fluid (CSF) biomarkers for AD and PD, with a particular emphasis on applicability to clinical trials. Compared with AD, less is known about CSF biomarkers in PD, and the authors highlight several areas for further research.

After brain injuries, microglia and macrophages can aid or hinder tissue repair depending on polarization toward specific cell phenotypes. This Perspectives article describes the phenotypic dynamics and different functions of these cells after acute CNS injury and argues that therapeutic approaches should focus on subtle adjustment of the balance between their phenotypes.