New HSF1 inducer as a therapeutic agent in a rodent model of Parkinson's disease.
Exp Neurol
; 306: 199-208, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-29704482
ABSTRACT
Molecular chaperone HSP70 (HSPA1A) has therapeutic potential in conformational neurological diseases. Here we evaluate the neuroprotective function of the chaperone in a rat model of Parkinson's disease (PD). We show that the knock-down of HSP70 (HSPA1A) in dopaminergic neurons of the Substantia nigra causes an almost 2-fold increase in neuronal death and multiple motor disturbances in animals. Conversely, pharmacological activation of HSF1 transcription factor and enhanced expression of inducible HSP70 with the echinochrome derivative, U-133, reverses the process of neurodegeneration, as evidenced by а increase in the number of tyrosine hydroxylase-containing neurons, and prevents the motor disturbances that are typical of the clinical stage of the disease. The neuroprotective effect caused by the elevation of HSP70 in nigral neurons is due to the ability of the chaperone to prevent α-synuclein aggregation and microglia activation. Our findings support the therapeutic relevance of HSP70 induction for the prevention and/or deceleration of PD-like neurodegeneration.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Cetirizina
/
Fármacos Neuroprotetores
/
Fatores de Transcrição de Choque Térmico
/
Antiparkinsonianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Exp Neurol
Ano de publicação:
2018
Tipo de documento:
Article
País de publicação:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA