Olfactory dysfunction and its related molecular mechanisms in Parkinson's disease

Changes in olfactory function are considered to be early biomarkers of Parkinson's disease. Olfactory dysfunction is one of the earliest non-motor features of Parkinson's disease, appearing in about 90% of patients with early-stage Parkinson's disease, and can often predate the diagnosis by years. Therefore, olfactory dysfunction should be considered a reliable marker of the disease. However, the mechanisms responsible for olfactory dysfunction are currently unknown. In this article, we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson's disease. On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels, we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson's disease. The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson's disease. Therefore, therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson's disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms, highlighting the potential of identifying effective targets for treating Parkinson's disease by inhibiting the deterioration of olfactory dysfunction.