Parkinson’s disease

In the 200 years since Parkinson's disease was first described, the understanding and management of the disease has come a long way. But researchers have yet to unlock all of its secrets. By Liam Drew.

Biomarkers will be essential if research on Parkinson's is to progress, but their discovery depends on scientists sharing data, says Mark Frasier.

Non-motor symptoms such as sleep disorders and a poor sense of smell may hold the key to diagnosing Parkinson's disease before the characteristic tremor starts.

By bootstrapping existing technologies, researchers can gain a minute-by-minute understanding of a patient's disease.

Deep brain stimulation is a proven treatment for Parkinson's disease. The only thing left to find out is how it works.

A controversial theory that could revolutionize our understanding of Parkinson's disease is gaining ground. But not everybody is convinced that misfolded proteins that spread in the brain are the cause of the disease.

The characteristic brain pathology and motor symptoms of Parkinson's disease are well established. But the details of the disease's cause and course are much murkier.

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.

An ultra-high-resolution structure of the core segment of assembled α-synuclein — the protein that aggregates in the brains of patients with Parkinson's disease — has been determined. A neurobiologist and a structural biologist discuss the implications of this advance. See Article p.486

Surprising events affect ongoing behaviour and cognitive processing, yet the underlying neural mechanisms remain unclear. Wessel and colleagues show that surprise recruits a motor suppression mechanism which may be implemented via the sub-thalamic nucleus and interrupts working memory performance.

Brain α-synuclein deposits are the hallmark of various distinct neurodegenerative diseases, and it is proposed that α-synuclein assemblies with different structural characteristics or 'strains' (ribbons or fibrils) could account for pathological differences between these diseases; here different human α-synuclein strains are injected into rat brain, and are shown to propagate in a strain-dependent manner and cause different pathological and neurotoxic phenotypes.

Numerous neurodegenerative diseases show deposition of protein aggregates, which are thought to cause neuronal damage. This Review discusses how cell-to-cell transmission of these pathogenic misfolded proteins is involved in initiation and progression of the disease and examines the clinical relevance of different strains in the heterogeneity of neurodegenerative disorders.

Parkinson disease is defined by its motor symptoms, but onset of nonmotor symptoms, including constipation, can start much earlier. In this Review, Klingelhoefer and Reichmann present the evidence that the pathogenesis of Parkinson disease starts in the gut and is transferred to the CNS via trans-synaptic cell-to-cell transport that initiates a cascade of α-synuclein aggregation. They also consider how this process might be triggered by environmental factors, and how these earliest stages of pathogenesis might be targeted to delay or prevent disease progression.