Токсичні моделі паркінсонізму: історія та перспективи

Abstract

The review article presents data on the history of research of extrapyramidal system dysfunctions, modern ideas about the etiology and diagnosis of Parkinson's disease, as the most common disease of the group of extrapyramidal disorders. Currently, no concept of effective therapy for patients with extrapyramidal system dysfunction has been developed, but it has been proven that the probability of developing the disease largely depends on the genetic predisposition and the level of environmental pollution. In the early stages, the disease is slow and asymptomatic, but gradually more than half of patients with Parkinson's disease die, and others need outside care. According to experts, in the near future, Parkinson's disease will become a problem for a significant part of people, because today it affects more and more people of working age. Under such conditions, reliable and early diagnosis of the disease is of great importance, which guarantees timely and most effective treatment. Modern therapies fail to stop the progressive death of the dopaminergic neurons of the substantia nigra, but traditional treatment can achieve symptomatic relief. Currently, it is known that the probability of developing Parkinson's disease depends on the genetic predisposition and the level of man-made environmental stress. The researchers consider that the pathological development of Parkinson's disease in the brain begins in the lower structures of the brain stem with the involvement of the caudal-Rostral nuclei, as well as the involvement of the cortico-basal ganglia-cerebellar pathways. The pathological process affects the ascending pathways and gradually passes to the midbrain, directly to the black substance, spreads from there and weakens the mesocortex and neocortex. Injuries in the brain stem lead to disorganization of the cortico-basal ganglia and cerebellar pathways, followed by the formation of alternative pathways to compensate for the initial disorders in the early stages of the disease. In addition, in Parkinson's disease, intracellular Lewy bodies and neurites formed by the protein alpha-synuclein are created, which are found in the autopsy material of most patients. Poor results of diagnostic evaluation and treatment of Parkinson's disease are usually associated with a lack of understanding of the pathogenesis of Parkinson's disease. The study of the biological basis and pathogenesis of Parkinson's disease is an important task of a whole complex of scientific studies of extrapyramidal system dysfunction. Conclusion. The article discusses the creation of toxic models of Parkinson's disease in vivo and in vitro, which help to recreate the pathogenesis of the disease for early diagnosis and the development of new ways to treat neurodegenerative diseases. In toxic models of Parkinsonism, not only deficits of motor functions such as bradykinesia, tremor, and posture disorders are actively studied, but also non-motor symptoms such as sleep disorders, neuropsychiatric and cognitive abnormalities