Exploring the Role of ACE2 as a Connecting Link between COVID-19 and Parkinson's Disease

Coronavirus disease 2019 (COVID-19) is frequently accompanied by neurological manifestations such as headache, delirium, and epileptic seizures, whereas ageusia and anosmia may appear before respiratory symptoms. Among the various neurological COVID-19-related comorbidities, Parkinson's disease (PD) has gained increasing attention. Some cases of PD disease have been linked to COVID-19, and both motor and non-motor symptoms in Parkinson's disease patients frequently worsen following SARS-CoV-2 infection. Although it is still unclear whether PD increases the susceptibility to SARS-CoV-2 infection or whether COVID-19 increases the risk of or unmasks future cases of PD, emerging evidence sheds more light on the molecular mechanisms underlying the relationship between these two diseases. Among them, angiotensin-converting enzyme 2 (ACE2), a significant component of the renin-angiotensin system (RAS), seems to play a pivotal role. ACE2 is required for the entry of SARS-CoV-2 to the human host cells, and ACE2 dysregulation is implicated in the severity of COVID-19-related acute respiratory distress syndrome (ARDS). ACE2 imbalance is implicated in core shared pathophysiological mechanisms between PD and COVID-19, including aberrant inflammatory responses, oxidative stress, mitochondrial dysfunction, and immune dysregulation. ACE2 may also be implicated in alpha-synuclein-induced dopaminergic degeneration, gut-brain axis dysregulation, blood-brain axis disruption, autonomic dysfunction, depression, anxiety, and hyposmia, which are key features of PD.