Disbiosi del microbiota intestinale e insorgenza del morbo di Parkinson

Parkinson's disease is the second most prevalent neurodegenerative disorder globally, ranking just after Alzheimer's disease. It primarily affects individuals over the age of 60, a demographic that is growing worldwide. The disease is characterized by a spectrum of symptoms, including motor impairments like tremors, rigidity, and bradykinesia, along with non-motor symptoms such as cognitive decline, sensory disturbances, and psychiatric issues. Pathologically, Parkinson's disease involves the progressive loss of dopaminergic neurons in the substantia nigra region of the brain and the accumulation of Lewy bodies, which are protein aggregates primarily composed of α-synuclein. These pathological hallmarks contribute to neuronal dysfunction and eventual cell death. Research has also highlighted the role of the gut-brain axis, suggesting that α-synuclein aggregates originating in the gut may travel to the brain via this pathway, exacerbating neurodegeneration. While the exact cause of Parkinson's disease remains unknown, genetic predispositions and environmental factors such as smoking, caffeine consumption, and exposure to pesticides have been implicated. The disease's progression involves a cascade of mechanisms, including abnormal protein aggregation (particularly α-synuclein), mitochondrial dysfunction, impaired protein clearance systems (ubiquitin-proteasome and autophagy-lysosome pathways), and neuroinflammation. Current treatments primarily focus on alleviating symptoms, with levodopa being the most common medication to replenish dopamine levels in the brain. However, these treatments do not halt disease progression nor effectively manage non-motor symptoms, highlighting the need for novel therapeutic approaches. Recent studies have underscored the potential role of gut microbiota in Parkinson's disease. Gut dysbiosis, characterized by alterations in microbial composition and function, has been observed in patients and is associated with increased gut permeability and systemic inflammation. This dysbiosis may contribute to disease pathogenesis by facilitating the entry of inflammatory microbial products into the systemic circulation, triggering neuroinflammation, and promoting the aggregation of α-synuclein in the brain. Therapeutic strategies targeting the gut microbiota have shown promise in preclinical and clinical studies. These include probiotics, prebiotics, fecal microbiota transplantation and diet interventions. These approaches aim to restore microbial balance, reduce inflammation, and potentially slow disease progression. Despite these advancements, challenges remain in identifying specific microbial populations that contribute to disease development and in translating microbiota-targeted therapies into effective clinical treatments. Future research efforts are focused on refining diagnostic tools, elucidating the pathways linking gut dysbiosis to Parkinson's pathology, and conducting larger-scale clinical trials to evaluate the safety and efficacy of microbiota-based interventions. In conclusion, while Parkinson's disease poses significant challenges due to its complex etiology and progressive nature, ongoing research into the gut-brain axis and microbiota offers promising avenues for developing novel therapeutic strategies. These efforts hold the potential to not only mitigate symptoms but also delay disease progression and improve the overall quality of life for individuals affected by Parkinson's disease.