Olfactory Neuron Substance P is Overexpressed in Parkinson's Disease Reflecting Gut Dysfunction

Parkinson’s disease motor progression in relation to the timing of REM sleep behavior disorder presentation: an exploratory retrospective study

“…PD is a heterogeneous syndrome characterized by the misfolding, aggregation, and subsequent cell-to-cell propagation of pathological α -synuclein inclusions, which share some similarities with prions (Conti et al 2022 ). According to the recent “α-Synuclein Origin and Connectome Model (SOC Model)” of PD, the α -synuclein pathology starts in a single location, the body, or the brain, and then propagates symmetrically or asymmetrically, depending on the origin of the accumulation, defining two types of PD: a “brain first” subtype and a “body first” subtype (Grillo et al 2022 ; Horsager et al 2022 ; Bovenzi et al 2023 ; Schirinzi et al 2023 ).…”

RNA sequencing of olfactory bulb in Parkinson's disease reveals gene alterations associated with olfactory dysfunction

“…One may speculate that in early stages, neurons have not died yet and less pronounced changes related to neuronal death and synaptic dysfunction may be observed while changes reflecting a higher inflammatory response may be observed. Interestingly, inflammatory mediators have been shown to be elevated in nasal mucosa samples collected from nasal brushings of PD subjects at early stages of the disease ( Schirinzi et al, 2023a , 2023b ). This underscores the importance of the early inflammatory response which may affect olfactory neurotransmission and the regeneration capacity of olfactory sensory neurons in early disease stages.…”

“…Additionally, activation of neuroinflammatory pathways have been repeatedly reported in PD ( Pajares et al, 2020 ; Isik et al, 2023 ) and findings of inflammation including microgliosis ( Kohl et al, 2017 ) and astrogliosis ( Flores-Cuadrado et al, 2021 ; Murray et al, 2022 ) were previously reported in post-mortem olfactory bulb of PD subjects. In the olfactory mucosa of living PD subjects, higher expression of inflammatory mediators was correlated with synucleinopathy markers ( Schirinzi et al, 2023a , 2023b ). Using single-cell RNA sequencing of the olfactory mucosa in Alzheimer’s disease further revealed alterations in inflammatory processes, protein metabolism and signal transduction in multiple cell populations ( Lampinen et al, 2022 ).…”

Acupuncture for Parkinson's disease-related constipation: current evidence and perspectives

“…The other is “body-first,” which starts with abnormal gut microbiota or inflammation in the gastrointestinal tract, leading to enteric neuron death and α-synuclein deposition, ultimately affecting dopamine neurons, and the motor control center. Substance P is overexpressed in the olfactory neurons of PD patients possibly due to gut dysfunction and is relevant to the discussion of prodromal constipation ( 18 ). This supports the idea that the gut plays an important role in PD and that prodromal constipation may be an early sign of the disease.…”