PARKINSON'S DISEASE: MULTISYSTEM APPROACH, PATHOGENESIS, AND MODERN TREATMENT STRATEGIES

Parkinson's disease has undergone significant conceptual changes in recent decades. This pathology, previously considered primarily as a dopamine deficiency disease with motor disorders, is now interpreted as a complex multisystem disease that develops as a result of the interaction of genetic predisposition, environmental factors, and aging processes. In addition to dopamine deficiency, α-synuclein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation play an important role in the pathogenesis of the disease. Recent scientific evidence indicates that Parkinson's disease may not be limited to the central nervous system but may progress through the gut-brain axis. In particular, intestinal microbiota imbalance, impaired intestinal wall patency, and the spread of pathological proteins through the blood-brain barrier are important in the early stages of the disease. At the same time, non-anomotor symptoms observed in the prodromal period expand the possibilities for early detection of the disease. Clinically, Parkinson's disease manifests as motor (tremor, rigidity, bradykinesia, postural instability) and non-motor (pain, depression, cognitive impairment, sleep and autonomic dysfunction) symptoms. Diagnosis is primarily based on clinical assessment, and the current lack of standard biomarkers complicates early diagnosis. In treatment, levodopa is still the most effective agent, and it is often used in combination with dopamine agonists, MAO-B inhibitors, and other drugs. In advanced stages of the disease, instrumental and surgical methods such as deep brain stimulation and focused ultrasound yield effective results. Recent advancements include molecular profiling, neuroimaging, and artificial intelligence-based analysis methods, which contribute to a deeper understanding of Parkinson's disease as a multifactorial systemic disease. Current research focuses on an individualized approach (precision medicine), biomarker identification, and the development of disease-modifying therapies. Physical activity is also an important component in disease management, allowing for the reduction of symptoms, the maintenance of neuroplasticity, and the slowing down of disease progression. In conclusion, Parkinson's disease is a complex and multifactorial disease, and its effective management requires a multidisciplinary, biomarker-based, and patient-centered approach.