Reviews & Analysis

MicroRNAs (miRNAs) seem to confer a novel layer of gene regulation, possibly fine-tuning the expression of ≈50% of genes in humans. Dysfunction of these short regulatory RNAs has been noted in various neurological disorders, including Alzheimer disease and Parkinson disease. Here, Junker and colleagues explore the possible involvement of miRNAs in multiple sclerosis, highlighting the therapeutic implications for this disease.

Protein misfolding and aggregation occur in most neurodegenerative disorders, but the concept of spreading and infectivity of aggregates in the CNS has, until recently, been confined to prion diseases such as Creutzfeldt–Jakob disease. New evidence suggests that prion-like spreading, involving proteins such as amyloid-β, tau, huntingtin and α-synuclein, can occur in other neurodegenerative disorders. In this article, Lee et al. discuss the underlying molecular mechanisms and consider the therapeutic implications of the new data.

In the past, neuropathic pain in patients with diabetes has been largely attributed to hyperexcitability of peripheral nerves, but a key role for central mechanisms has emerged from studies conducted over the past 5 years. In this article, Fischer and Waxman discuss findings that implicate thalamic neurons in the central generation and amplification of pain in diabetes.

Activated microglia are a feature of many neurodegenerative disorders, including amyotrophic lateral sclerosis and Alzheimer disease. Conflicting results exist, however, for the effectiveness of anti-inflammatory drugs in such conditions. In this article, Schwartz and Shechter propose a model that describes the complexities of the immune response in neurodegenerative diseases and offer an explanation for why such drugs have so far yielded inconsistent data in this setting.

Practicing clinicians can experience difficulty in differentiating between Parkinson disease and idiopathic normal pressure hydrocephalus. In this article, Morishita and colleagues consider the clinical features that might differentiate Parkinson disease from idiopathic normal pressure hydrocephalus, and highlight the usefulness of the levodopa challenge test in distinguishing between these two conditions.