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. 2021 Aug 15:194:108378.
doi: 10.1016/j.neuropharm.2020.108378. Epub 2020 Nov 6.

Celecoxib promotes survival and upregulates the expression of neuroprotective marker genes in two different in vitro models of Parkinson's disease

Sarah Dassati  1 , Rüdiger Schweigreiter  2 , Susanne Buechner  3 , Andreas Waldner  4
Affiliations

Celecoxib promotes survival and upregulates the expression of neuroprotective marker genes in two different in vitro models of Parkinson's disease

Sarah Dassati et al. Neuropharmacology. .

Abstract

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease. Increasing evidence highlights the role of age-related chronic inflammation, oxidative stress and mitochondrial dysfunction in the pathogenesis of PD. A combination of these factors impairs the crosstalk between mitochondria and lysosomes, resulting in compromised cell homeostasis. Apolipoprotein D (APOD), an ancient and highly conserved anti-inflammatory and antioxidant lipocalin, and the transcription factor EB (TFEB), a master regulator of mitophagy, autophagy and lysosomal biogenesis, play key roles in these processes. Both APOD and TFEB have attracted attention as therapeutic targets for PD. The aim of this study was to investigate if the selective cyclooxygenase-2 inhibitor celecoxib (CXB) exerts a direct neuroprotective effect in 6-hydroxydopamine (6-OHDA) and paraquat (PQ) PD models. We found that CXB rescued SH-SY5Y cells challenged by 6-OHDA- and PQ-induced toxicity. Furthermore, treatment with CXB led to a marked and sustained upregulation of APOD and the two microphthalmia transcription factors TFEB and MITF. In sum, this study highlights the clinically approved drug CXB as a promising neuroprotective therapeutic tool in PD research that has the potential to increase the survival rate of dopaminergic neurons that are still alive at the time of diagnosis.

Keywords: 6-Hydroxydopamine; Apolipoprotein D; Celecoxib; Cyclooxygenase-2; Microphthalmia transcription factors; Neuroprotection; Paraquat; Parkinson's disease; Transcription factor EB (TFEB).

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