Objective: To elucidate the role of Substance P in PD through molecular characterization of patients’ olfactory neurons.

Background: Substance P is a neuropeptide largely expressed in the gastrointestinal-nervous ascending pathway in response to several triggers. Substance P can mediate detrimental neuroinflammatory processes involved in PD pathogenesis, although no direct proof exists yet.  Olfactory neurons mirror central neuropathology, permitting to dissect molecular events underlying the clinical-pathological dynamics of PD in vivo.

Method: Olfactory neurons were collected from 30 patients and 20 sex/age-matched healthy controls through mucosa brushing. Substance P and the NK1 receptor gene expression levels were comparatively quantified by the Real Time-PCR; moreover, immunofluorescence staining to measure Substance P was performed. In patients, biochemical data were correlated with main clinical scores, including the Gastrointestinal Dysfunction Scale for Parkinson’s Disease and the presence of constipation.

Results: Olfactory neurons from PD patients overexpressed Substance P. The expression increased in parallel with the gastrointestinal dysfunction, including constipation. NK1 receptor levels, instead, were similar between patients and controls.

Conclusion: Olfactory neurons Substance P overexpression in association with gastrointestinal dysfunction suggests a main role for this tachykinin in PD pathogenesis. Substance P might represent a mediator of the “body-first” trajectory, serving either as a specific biomarker or a novel therapeutic target.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/olfactory-neurons-substance-p-is-highly-expressed-in-parkinsons-disease-reflecting-gastrointestinal-dysfunction/