Monoamine Oxidase Inhibitors in Drug Discovery Against Parkinson’s Disease: A Brief Review

Parkinson's disease (PD) is a progressive neurodegenerative disease whose symptoms include tremors, gastrointestinal and motor disorders, bradykinesia, depression, sleep disorders, and pain. Currently, after Alzheimer’s Disease, PD is the second most common ND worldwide, with great socioeconomic impact, as it affects people of working age, slowly progresses to a disability, and dementia, remaining incurable to date. The PD pathophysiology is complex and multifactorial, characterized by a progressive loss of dopaminergic neurons, and dopamine deficits, especially in regions of the central nervous system (CNS) related to motor skills and coordination. In addition, the literature is rich in data that suggests the deposition of poorly processed α-synuclein protein fragments, which generate fibril aggregates, known as Lewy’s bodies, into the neuronal cytosol, besides reduced dopamine availability, neuroinflammation, and oxidative stress (OS). The clinical management of PD remains a challenge, with a limited available drug arsenal, low efficacy and the occurrence of tolerance in most cases, requiring the practice of polypharmacology to address the different stages of the disease, including antidepressants and anxiolytics. PD, like other NDs, has a very complex pathogenesis, still not fully understood, given its multifactoriality and the concomitant and interconnected dysfunction of several biochemical pathways and cellular events. In this context, among the diverse molecular targets studied for potential modulation and most effective pharmacological intervention, monoamine oxidase (MAO) isoforms A and B, especially MAO-B, have attracted special attention from the scientific community. This work aims to review the most recent data in the literature regarding the role of MAO in the PD pathophysiology, and the Medicinal Chemistry advances in identifying MAO inhibitors as new drug candidates against PD.