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Dysregulated cytokine networks are important in the pathogenesis of neuroinflammation. This Review discusses targeting cytokines and their receptors in non-infectious central nervous system inflammatory diseases such as multiple sclerosis and neurosarcoidosis, as well as in the neurotoxic adverse events that can be triggered by cancer immunotherapy.
Targeting the interactions between neurons, cancer cells and other elements in the tumour microenvironment represents a potential paradigm shift in cancer treatment. This Review article provides an overview of the dynamics of the nerve–cancer cell interplay as well as a discussion of current preclinical and clinical evidence of the benefits of targeting the nervous system in cancer.
Multiple protein isoforms arise from most genes by alternative RNA splicing and other mechanisms, but these isoforms are often neglected in drug discovery. This Review discusses the modes of action of emerging therapeutics that focus on protein isoforms as well as how isoforms can serve as biomarkers and facilitate targeted drug delivery.
The M1 and M4 muscarinic acetylcholine receptors represent promising therapeutic targets for Alzheimer disease and schizophrenia. However, the development of agents targeting these receptors has been limited by their adverse cholinergic effects. Here, Tobin discusses how recent advances in the field — including an increased understanding of receptor biology and signalling, as well as the application of structure-based drug design — are enabling a new generation of muscarinic receptor modulators to enter clinical development.