Transcutaneous vagus nerve stimulation (tVNS) as a potential therapeutic application for neurodegenerative disorders - A focus on dysautonomia in Parkinson's disease.

The understandings of pathogenic processes in major neurodegenerative diseases has significantly advanced in recent years, with evidence showing pathological spread of intraneuronal proteinaceous inclusions as a fundamental factor. In Parkinson's disease (PD), the culprit protein has been identified as α-synuclein as the main component for mediating progressive neurodegeneration. With severe pathology evident in the autonomic nervous system prior to clinical manifestations of PD, pathogenic spread can occur from the peripheral nervous system through key nuclei, such as the anterior olfactory nucleus and dorsal motor nucleus of the glossopharyngeal and vagal nerves, gradually reaching the brainstem, midbrain and cerebral cortex. With this understanding and the proposed involvement of the vagus nerve in disease progression in PD, notably occurring prior to characterized clinical motor features, it raises intriguing questions as to whether vagal nerve pathology can be accurately detected, and importantly used as a reliable marker for determining early neurodegeneration. Along with this is the potential use of vagus nerve neuromodulation for treatment of early disease symptoms like dysautonomia, for modulating sympatho-vagal imbalances and easing severe comorbidities of the disease. In this article, we take a closer look at the pathogenic transmission processes in neurodegenerative disorders that impact the vagus nerve, and how vagus nerve neuromodulation can be potentially applied as a therapeutic approach for major neurodegenerative disorders.