THE PATHOGENETIC ASPECTS OF PARKINSON'S DISEASE AND POSSIBLE WAYS OF THEIR CORRECTION
DOI:
https://doi.org/10.34287/MMT.4(47).2020.6Abstract
Purpose of the study. The purpose of the work is to summarize the data available in the literature regarding the role of shock proteins, in particular the HSP 70 protein, in the mechanisms of endogenous neuroprotection and neurodegradation in Parkinson's disease (PD). The article also aims at determining the possible pathogenetic stages of the disease development and the place of mitochondrial dysfunction, apoptotic and antiapoptotic systems in these processes. The modulation of PD MPTP model can help to identify possible ways of influencing the pathogenetic mechanisms of neurodegenerative changes in structures of the extrapyramidal system by stimulating the processes of neuroprotection and slowing of neurodegradation owing to inducing protein level synthesis. After statistical processing of the obtained results, one can interpolate the obtained data on idiopathic PD in the population by matching the relevant neurodegenerative process markers found in the experiment with indicators in PD patients. As a result, it may hypothetically be possible to develop the use of personalized pathogenetic therapy for PD.
References
Dolgacheva LP. [Alpha-synuclein and mitochondrial dysfunction in Parkinson's disease]. Biologicheskiye membrany: Zhurnal membrannoy i kletochnoy biologii. 2017; 34 (5): 4–14. Russian.
Belenichev IF. [Neuroprotection and neuroplasticity]. Logos. 2015. 510 P. Russian.
Orlova EV. [The role of apoptosis regulatory proteins]. Khimiko-farmatsevticheskii zhurnal. 2005; 39 (12): 3–8. Russian.
Petukhova IS, Vasilieva OA, Bondar OB. [Parkinson's disease and complex drug therapy in the early stages of the disease]. Yeksperimental'na í klíníchna meditsina. 2018; 2–3 (79–80): 111–116. Russian.
Faller DM, Shilds D. [Molecular biology of the cell]. Moscow, BINOM Publ. 2006. 256 P. Russian.
Chistik T. [Cholinergic strategy in the treatment of cognitive impairment in aging]. Mezhdunarodnyy nevrologicheskiy zhurnal. 2015; 2 (72): 147–152. Russian.
Tsybko AS. [The effect of atypical antipsychotic drugs on the expression of neurotrophic factor genes in an MPTP-induced model of Parkinson's disease]. Neyrokhimiya. 2019; 36 (2): 155–163. Russian. DOI: 10.1134/ S1027813319020122.
Accumulation of toxic α-synuclein oligomer within endoplasmic reticulum occurs in α-synucleinopathyinvivo/CollaE.etal.J.Neurosci. 2012. Vol.32, No.10. P. 3301-3305. DOI: https:// doi.org/10.1523/JNEUROSCI.5368-11.2012.
Angelova P. R., Abramov A. Y. Alphasynuclein and beta-amyloid different targets, same players: calcium, free radicals and mitochondria in the mechanism of neurodegeneration. Biochem. Biophys. Res. Commun. 2017. Vol. 483, № 4. P. 1110–1115. DOI: 10.1016/j.bbrc.2016.07.103.
Bcl-2 inhibits nuclear homologous recombination by localizing BRCA1 to the endomembranes/ Laulier C. et al. Cancer Res. 2011. Vol. 71, № 10. P. 590-602. DOI: 10.1158/00085472.CAN-10-3119.
Dauer W., Przedborski S. Parkinson’s disease: mechanisms and models. Neuron. 2003. Vol. 39, № 6. P. 889–909. DOI: 10.1016/s08966273(03)00568-3
Expression changes of genes associated with apoptosis and survival processes in Parkinson’s disease/ Yalçınkaya N. et al. Neurosci. Lett. 2016. Vol. 615. P. 72–77. DOI: 10.1016/j.neulet.2016.01.029.
Gopalakrishna R., Jaken S. Protein kinase C signaling and oxidative stress // Free Radic. Biol. Med. 2000. Vol. 28. P. 1349–1361. DOI: 10.1016/ s0891-5849(00)00221-5.
Hsp70 protein complexes as drug targets/ Assimon V. A. et al. Curr Pharm Des. 2013. Vol. 19, № 3. P.404–417. DOI: 10.2174/138161213804143699.
Inhibition of stress-inducible HSP70 impairs mitochondrial proteostasis and function/ Leu J. I. et al. Oncotarget. 2017. Vol. 8, № 28. P. 45656–45669. DOI: 10.18632/ oncotarget.17321.
Kim J. Y., Yenari A. Heat Shock Proteins and the Stress Response/ Primer on Cerebrovascular Diseases (Second Edition). 2017. 968 p. Chapter 56. рр. 273–275.
Nitration of Hsp90 induces cell death/ Franco M. C. et al. Proc. Natl. Acad. Sci. 2013. Vol. 110, № 2. P. 1102–1111. DOI: 10.1073/ pnas.1215177110.
Sharp F. R., Zhan X., Liu D. Z. Heat shock proteins in the brain: role of Hsp70, Hsp 27, and HO-1 (Hsp32) and their therapeutic potential/ Transl Stroke Res. 2013. Vol. 4, № 6. P. 685–692. DOI: 10.1007/s12975-013-0271-4.
Structural basis for the inhibition of HSP70 and DnaK chaperones by small-molecule targeting of a C-terminal allosteric pocket/ Leu J. I. et al. ACS Chem Biol. 2014. Vol.9. P. 2508–2516. DOI: 10.1021/cb500236y.
When melatonin gets of your nerves: its beneficial actions in experimental models of stroke/ Reiter R.J. et al. Exp. Biol. Med. 2005. V. 230. P. 104–117. DOI: 10.1177/153537020523000205.
