RGD Reference Report - Modulatory effects of sodium salicylate on the factors affecting protein aggregation during rotenone induced Parkinson's disease pathology. - Rat Genome Database

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Modulatory effects of sodium salicylate on the factors affecting protein aggregation during rotenone induced Parkinson's disease pathology.

Authors: Thakur, P  Nehru, B 
Citation: Thakur P and Nehru B, Neurochem Int. 2014 Sep;75:1-10. doi: 10.1016/j.neuint.2014.05.002. Epub 2014 May 19.
RGD ID: 10402545
Pubmed: PMID:24852355   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuint.2014.05.002   (Journal Full-text)

Sodium salicylate (SS) confers neuroprotection in various models of Parkinson's disease (PD) but the mechanisms behind its protective actions are not clear. PD pathology is multifactorial involving numerous processes such as protein aggregation, dysfunction of protein degradation machinery and apoptosis. Detailed evaluation of effects of SS on these processes can provide an insight into the mechanism of neuroprotection by SS in PD pathology. In a rotenone (2mg/kg b.w.) based rat model of PD, SS (100mg/kg b.w.) was administered in conjunction. Drug treatments continued for 5 weeks after which various analyses were conducted using mid-brain tissue. IHC analysis revealed a decline in the aggregation of alpha-synuclein and ubiquitin with SS supplementation. These effects might be mediated by the elevation in HSF-1, HSP-40, and HSP-27 expression following SS co-treatment. This HSP upregulation helped in the improvement in proteasome activity as well as expression. Further, IHC analysis revealed that SS co-treatment prevented the activation of astrocytes caused by rotenone. Since astrocytes are involved in maintenance of glutathione (GSH) homeostasis, it resulted in a concomitant improvement in the GSH levels. As a result, decrease in apoptosis as indicated by caspase-9 and caspase-3 expression as well as TUNEL assay was also observed in the SS conjunction group. Our results indicate that besides being a known free radical scavenger and anti-inflammatory compound, SS can provide neuroprotection by differently upregulating the HSPs and reducing the protein aggregation burden.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinson's disease treatmentISOHsf1 (Rattus norvegicus)10402545; 10402545 RGD 
Parkinson's disease treatmentIDA 10402545 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hsf1  (heat shock transcription factor 1)

Genes (Mus musculus)
Hsf1  (heat shock factor 1)

Genes (Homo sapiens)
HSF1  (heat shock transcription factor 1)


Additional Information