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

Authors
  • Thakur, Poonam1
  • Nehru, Bimla2
  • 1 Department of Biophysics, Panjab University, Chandigarh 160014, India. Electronic address: [email protected] , (India)
  • 2 Department of Biophysics, Panjab University, Chandigarh 160014, India. Electronic address: [email protected] , (India)
Type
Published Article
Journal
Neurochemistry international
Publication Date
Sep 01, 2014
Volume
75
Pages
1–10
Identifiers
DOI: 10.1016/j.neuint.2014.05.002
PMID: 24852355
Source
Medline
Keywords
License
Unknown

Abstract

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 α-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.

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