Alpha-synuclein pathology and Parkinson's disease-related olfactory dysfunctions: an update on preclinical models and therapeutic approaches.

Olfactory dysfunction (OD) is considered one of the early signs of Parkinson's disease (PD), affecting over 90% of PD patients. OD often appears several years before the onset of motor symptoms and is therefore considered an early biomarker of PD. Recent studies have shown that COVID-19 infection might lead to worsening of symptoms and acceleration of disease progression in neurodegenerative disorders, where OD is a common symptom to both. Hence, it is essential to accurately monitor olfactory fitness in clinical settings using any of the currently available olfactory function tests. Even after a quarter of a century of the discovery of α-synuclein (α-syn) pathogenesis in PD, many aspects related to the α-syn pathogenesis in OD remain unknown. Currently, there is no definitive cure for PD; the disease management options include dopaminergic medications, deep brain stimulations, stem cells, and immunotherapy. Generating reliable PD animal models is critical for understanding the molecular pathways and neural circuits affected by disease conditions. This might contribute to the development and validation of new therapeutic approaches. This review discusses the known mechanisms of α-syn aggregated forms causing neuronal death, the recent developments in the PD preclinical models with ODs, and the treatment strategies employed.