Exogenous protein HSP70 blocks neurodegeneration in the rat model of the clinical stage of Parkinson's disease

Autor: I. V. Ekimova, Yu. F. Pastukhov, Irina V. Guzhova, K. V. Lapshina, D. V. Plaksina
Rok vydání: 2014
Předmět:
Zdroj: Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections. 457(1)
ISSN: 1608-3105
Popis: According to modern views, impairment of protein folding is a serious danger for cell survival and a molecular basis for neurodegeneration (1, 2). A decrease in the activity of the ubiquitin proteasome system, which is responsible for disposal of misfolded proteins, may cause accumulation of toxic oligomers of α synuclein and degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars com� pacta (SNpc) and their axons in the striatum. This mechanism plays the key role in the pathogenesis of Parkinson's disease (PD) (3-6). This disease still has no cure due to commonly late diagnosis and symp� tomatic treatment, which cannot stop neuron death (7, 8). In recent years, the use of chaperones, particu� larly heat shock proteins of the 70�kDa family (HSP70), which are able to recover misfolded pro� teins, is considered as a promising therapeutic strategy, including treatment of PD (9-13). Neurons of SNpc during a moderate decrease in proteasome function survive mainly when they have increased content of inducible chaperone Hsp70i (14). The protective effects of exogenous Hsp70i in PD have not been stud� ied. The aim of this study was to investigate if intrana� sal administration of recombinant Hsp70i could atten� uate neurodegeneration and reduce motor impair� ment in the model of the clinical stage of PD. The rat model of a prolonged clinical stage of PD (up to 21 days) was created using the modern views on the molecular mechanisms of neurodegeneration by diminishing the proteasome activity in the nigrostri� atal system. The protective effects of exogenous Hsp70 were evaluated in this model. We discovered for the first time that intranasal administration of recombi� nant Hsp70 in the dynamics of clinical stage reduced the loss of DAergic neurons in SNpc by a factor of two and recovered motor functions. Our results can be used for further clinical study of chaperones drugs and their inductors elevating the Hsp70 level in the brain to develop methods of preventive treatment and to search new ways of blocking neurodegeneration at the clinical stage of PD. These results can be considered to be a priority. The study was carried out on male Wistar rats
Databáze: OpenAIRE
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