OBJECTIVE: To perform a comprehensive analysis of current data on selective neurodegeneration of dopaminergic substantia nigra neurons in Parkinson's disease. The focus is on genetic, environmental, and pathological factors - such as-synuclein, mitochondrial dysfunction, calcium imbalance, the gut-brain axis, uric acid, stress, and socio-economic influences. Advances in diagnostics and therapies to slow progression are also considered. α
MATERIAL AND METHODS: This review is based on a systematic review of publications (2020-2025) from the PubMed, Scopus, Cochrane, MedLine, and Google Scholar databases. Peer-reviewed studies on selective neurodegeneration of dopaminergic neurons in the substantia nigra in patients with Parkinson's disease are included, covering genetic, environmental, and pathological factors; diagnostic and therapeutic approaches; studies with patients and controls; and nonclinical models. Non-peer-reviewed papers, studies without a methodology described, and those that do not correspond to the topic or time criterion (before 2020) were excluded, except for basic sources.
RESULTS: The review showed that selective neurodegeneration of dopaminergic neurons in the substantia nigra is a key mechanism of Parkinson's disease, driven by a variety of factors ranging from genetic predisposition and mitochondrial dysfunction to pathological-synuclein aggregation, calcium imbalance, microbiota changes, and psychological stress. Early diagnosis is challenging; however, new biomarkers and neuroimaging methods can help detect the disease before clinical manifestation. Current therapeutic approaches focus on disease modification, including neuroprotection, targeted therapies, and cellular technologies. The integration of multidisciplinary data and the development of personalized medicine are promising areas for treating neurodegeneration. α
CONCLUSION: Parkinson's disease is a multifactorial neurodegenerative disease in which the selective neurodegeneration of dopaminergic neurons in the substantia nigra plays a key role. Current data emphasize the importance of early diagnosis and the development of disease-modifying therapies targeting the main pathogenic mechanisms. The integration of molecular, clinical, and socio-economic aspects is a promising direction for a personalized approach to treatment and improvement of patients' prognosis.
