IMPORTANCE OF THE GUT–BRAIN AXIS AS A NOVEL THERAPEUTIC TARGET IN THE MANAGEMENT AND TREATMENT OF PARKINSON'S DISEASE

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder, recognized as the second most common neurodegenerative disease globally, primarily impacting older adults. Neuropathologically, it is defined by the selective degeneration of dopaminergic neurons located in the substantia nigra pars compacta, alongside the intracellular buildup of misfolded α-synuclein protein, which forms Lewy bodies and Lewy neurites. Lewy pathology is identified in up to 90% of clinically diagnosed PD cases and extends beyond the nigrostriatal system, affecting brainstem nuclei, peripheral autonomic regions, the limbic system, and neocortical areas. There is growing evidence indicating that α-synuclein pathology may initiate years prior to the emergence of classical motor symptoms, impacting areas such as the gastrointestinal tract, olfactory structures, and the autonomic nervous system. The incidence and prevalence of PD rise with age, exhibiting a male predominance of approximately 2:1. While PD has been reported more frequently in White populations, postmortem studies reveal a similar prevalence of Lewy bodies across different racial groups. Mortality rates for PD are significantly elevated compared to the general population, and the socioeconomic impact of PD is considerable, with healthcare expenses expected to increase dramatically in the forthcoming decades. The etiology of PD is complex, involving a combination of genetic and environmental factors. Monogenic forms represent about 20% of cases and include autosomal dominant variants such as LRRK2, GBA1, and SNCA, as well as autosomal recessive variants like PRKN, PINK1, and DJ-1. Environmental factors, particularly exposure to pesticides and industrial solvents, have been strongly linked to an increased risk of developing PD, likely through mechanisms related to mitochondrial dysfunction and oxidative stress. Additionally, epigenetic regulation, including histone modifications that influence SNCA expression, plays a significant role in disease susceptibility. Recent research underscores the essential role of the brain–gut–microbiota axis in the pathophysiology of PD.