Journal of Alzheimer's Disease
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Home > Neuroprotective Effect of Phloretin in Rotenone-Induced Mice Model of Parkinson's Disease: Modulating mTOR-NRF2-p62 Mediated Autophagy-Oxidative Stress Crosstalk.

TitleNeuroprotective Effect of Phloretin in Rotenone-Induced Mice Model of Parkinson's Disease: Modulating mTOR-NRF2-p62 Mediated Autophagy-Oxidative Stress Crosstalk.
Publication TypeJournal Article
Year of Publication2023
AuthorsShirgadwar, SM, Kumar, R, Preeti, K, Khatri, DKumar, Singh, SBala
JournalJ Alzheimers Dis
Volume94
Issues1
PaginationS109-S124
Date Published2023
ISSN1875-8908
KeywordsAnimals, Antioxidants, Autophagy, Humans, Kelch-Like ECH-Associated Protein 1, Mice, Mice, Inbred C57BL, Neuroblastoma, Neurodegenerative Diseases, Neuroprotective Agents, NF-E2-Related Factor 2, Oxidative Stress, Parkinson Disease, Phloretin, Prospective Studies, Rotenone, TOR Serine-Threonine Kinases
Abstract

BACKGROUND: Parkinson's disease (PD) is an age-related progressive multifactorial, neurodegenerative disease. The autophagy and Keap1-Nrf2 axis system are both implicated in the oxidative-stress response, metabolic stress, and innate immunity, and their dysregulation is associated with pathogenic processes in PD. Phloretin (PLT) is a phenolic compound reported possessing anti-inflammatory and antioxidant activities.

OBJECTIVE: To evaluate the neuroprotective potential of PLT in PD via modulating the autophagy-antioxidant axisMethods:The neuroprotective effect of PLT was evaluated in vitro using rotenone (ROT) exposed SH-SY5Y cell line and in vivo using ROT administered C57BL/6 mice. Mice were administered with PLT (50 and 100 mg/kg, p.o.) concomitantly with ROT (1 mg/kg, i.p) for 3 weeks. Locomotive activity and anxiety behaviors were assessed using rotarod and open field tests respectively. Further apoptosis (Cytochrome-C, Bax), α-Synuclein (α-SYN), tyrosine hydroxylase (TH), antioxidant proteins (nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1) and autophagic (mTOR, Atg5,7, p62, Beclin,LC3B-I/II) protein activity were evaluated both in in vitro and in vivo.

RESULTS: PLT improved locomotive activity and anxiety-like behavior in mice. Further PLT diminished apoptotic cell death, α-SYN expression and improved the expression of TH, antioxidant, and autophagic regulating protein.

CONCLUSION: Taken together, present data deciphers that the PLT effectively improves motor and non-motor symptoms via modulating the mTOR/NRF2/p62 pathway-mediated feedback loop. Hence, PLT could emerge as a prospective disease-modifying drug for PD management.

DOI10.3233/JAD-220793
Alternate JournalJ Alzheimers Dis
PubMed ID36463449
PubMed Central IDPMC10473071
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Source URL: https://www.j-alz.com/content/neuroprotective-effect-phloretin-rotenone-induced-mice-model-parkinsons-disease-modulating