Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus.

Objectives: Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial.

Clinicopathological case: progressive somnolence and dementia in an accountant: when the shine rubs off the gold standard.

A 63-year-old accountant developed progressive somnolence, cognitive decline, gait disturbance and cerebellar dysfunction with autonomic features. This report documents the clinicopathological conference at the 39th Edinburgh Advanced Neurology Course 2017.

Corticosteroids for acute ischaemic stroke.

Background: The majority of strokes are due to cerebral infarction. Ischaemic cerebral tissue tends to develop cytotoxic oedema which, if the blood-brain barrier is disrupted, may be followed by vasogenic oedema. Large infarcts can develop life-threatening massive oedema.

Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies.

Ubiquitin-positive intraneuronal inclusions are a consistent feature of the major human neurodegenerative diseases, suggesting that dysfunction of the ubiquitin proteasome system is central to disease etiology. Research using inhibitors of the 20S proteasome to model Parkinson's disease is controversial. We report for the first time that specifically 26S proteasomal dysfunction is sufficient to trigger neurodegenerative disease.

The ubiquitin-proteasome system and cancer.

The ubiquitin proteasome system (UPS) has emerged from obscurity to be seen as a major player in all regulatory processes in the cell. The concentrations of key proteins in diverse regulatory pathways are controlled by post-translational ubiquitination and degradation by the 26 S proteasome. These regulatory cascades include growth-factor-controlled signal-transduction pathways and multiple points in the cell cycle.