Abstract
Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the elderly. The aim of the study. To study apoptotic processes and their role in the formation of dopaminergic neurodegeneration and to develop new treatment regimens with a specific neuroprotective effect on the dopaminergic system. Materials and methods. The study was carried out on 90 Wistar rats at the age of 6 months weighing 220–290 grams. Parkinsonism was induced by the administration of the neurotoxin MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to experimental rats with neuroprotective treatment: I – Intact (passive control); II – animals with experimental Parkinson's disease (PD, active control); III – PD + Amantadine (AM) IV – PD + AM + Cerebrocurin; V – PD + AM + Pramistar; VI – PD + AM + Gliatilin; VII – PD + AM + Noofen; VIII – PD + AM + Pronoran; IX – PD + AM + Melatonin. Results. The obtained data indicate that neuroprotective therapy of PD with drugs such as melatonin, cerebrocurin, pronoran and gliatilin in combination with amantadine leads to an increase in the expression of the HIF-1α, HIF-3α, HSP70 genes, bcl-2 proteins and decrease c-fos proteins with caspase-3 as markers of apoptosis and can also serve as a molecular marker for the activation of endogenous neuroprotection mechanisms under the conditions of an experimental PD. Conclusions. The study experimentally demonstrated a new target of neuroprotection in PD conditions – apoptosis of dopamine-producing neurons and substantiated modulators of this process – drugs for combined therapy with amantadine (melatonin, cerebrocurin, pronoran and gliatilin) as promising drugs for the treatment of PD.
Highlights
MOLECULAR MARKERS OF ENDOGENOUS and the guidelines set out in in Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the elderly
After amantadine treatment of rats with Parkinson's disease (PD), the density of bcl-2-positive neurons increased compared to the control by 10.18 % (p≤0.05), in the group of cerebrocurin – by 23.71 % (p≤0.05), pramistar – 17.54 %, gliatilin – 21.71 % (p≤0.05), noophen – 18.60 %, pronoran – 19.73 %, melatonin – 26.13 %
Cerebrocurin has a complex neuroprotective effect due to its ability to stabilize the functional state of mitochondria and limit the development of mitochondrial dysfunction [4]; to prevent the formation of energy deficit; block the development of lactic acidosis against the background of activation of compensatory mitochondrial-cytosolic shunts of energy products, especially malate-aspartate; reduce the manifestations of oxidative and nitrosative stresses; modulate the expression of all isoforms of NOS, as well as HIF and HSP proteins; increase the activity of enzymes of the antioxidant and thiol-disulfide systems; morphologically stabilize neuronal and glial cells with parallel activation of RNA synthesis in them, as well as to restore the morphological ultrastructure of mitochondria; affect the processes of apoptosis/necrosis and due to the regulatory effect on the expression of c-fos
Summary
MOLECULAR MARKERS OF ENDOGENOUS and the guidelines set out in in Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the elderly. NEUROPROTECTION IN THE BRAIN OF RATS WITH EXPERIMENTAL PARKINSON'S DISEASE AND ON THE BACKGROUND OF USING NEW. PHARMACOTHERAPY SCHEMES “Basic principles of studying the toxicity of potential pharmacological drugs” (State Enterprise «Ukrainian Pharmaceutical Quality Institute», K., 2000). The expedopamine depletion caused by degeneration of dopaminergic neurons in the compact substantia nigra [1]. Apoptosis is the predominant mode of neuronal death. The verification for the strategy of rational therapy in PD was based on studying the acin many neurodegenerative dis- Abstract: Parkinson's disease (PD) is one of the most common tivity of drugs in groups of anieases, including PD. While the neurodegenerative diseases in the elderly
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