ArticleIranian journal of pharmaceutical research : IJPR2019
Trehalose Neuroprotective Effects on the Substantia Nigra Dopaminergic Cells by Activating Autophagy and Non-canonical Nrf2 Pathways.
Article in Iranian journal of pharmaceutical research : IJPR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Trehalose's untapped mechanisms in alzheimer's: gut-brain-autophagy signalling beyond the usual targets.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Exercise-Driven NRF2 Activation as a Systemic Neuroprotective Strategy: Integrating Redox Biology, Muscle-Brain Crosstalk, and Therapeutic Targeting in Neurodegeneration.Biochemical genetics · 2026Review
- Nrf2-Keap1 Pathway and NLRP3 Inflammasome in Parkinson's Disease: Mechanistic Crosstalk and Therapeutic Implications.Molecular neurobiology · 2025Review
- Review
- Trehalose Attenuates In Vitro Neurotoxicity of 6-Hydroxydopamine by Reducing Oxidative Stress and Activation of MAPK/AMPK Signaling Pathways.International journal of molecular sciences · 2024Article
- Profiling neuroprotective potential of trehalose in animal models of neurodegenerative diseases: a systematic review.Neural regeneration research · 2023Review
- A Pivotal Role of Nrf2 in Neurodegenerative Disorders: A New Way for Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Effects of trehalose on NFE2L2, catalase, and superoxide dismutase in the kidney of aged rats.Molecular biology research communications · 2022Article
- Therapeutics in the Pipeline TargetingPharmacological reviews · 2022Review
- NRF2 Activation and Downstream Effects: Focus on Parkinson's Disease and Brain Angiotensin.Antioxidants (Basel, Switzerland) · 2021Review
- Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson's Disease.Frontiers in pharmacology · 2021Review
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trehalose, as a natural disaccharide, is known as an autophagy inducer. The neuroprotective effects of trehalose in the rat model of Parkinson's disease were the aim of the present study. Parkinson's disease model was induced by injecting 6-hydroxydopamine (6-OHDA) in the striatum of male Wistar rats. Apomorphine-induced behavior and substantia nigra neuronal counts were applied to evaluate the neuroprotective effects of trehalose. The autophagy was studied using the expression of p62 and LC3II/LC3I ratio. In addition, the antioxidant effects of trehalose were assessed by analyzing the levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and also glutathione reductase (GR), glutathione peroxidase (GPx) and Catalase (CAT) enzymes. Moreover, the levels of 3, 4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) were assessed.The behavioral test showed that trehalose in the treatment group reduced the damage to the substantial nigra dopaminergic neurons, which was characterized by improved motor and reduced rotations in the treatment group as compared with the lesion group. In the histological examinations of the treatment group, trehalose prevented the destruction of dopaminergic neurons. Trehalose treatments increased autophagy (high LC3II/LC3I ratio) and the expression of the p62 protein as well. Through p62-dependent manner, it led to increased nuclear translocation of Nrf2 transcription factor and elevated expression of downstream antioxidant enzymes, such as GR, GPx, and CAT, restoring DA and DOPAC contents of the cells. In the current study, trehalose simultaneously protects substantia nigra dopaminergic cells by activating both non-canonical p62/SQSTM1-Keap1-Nrf2 and autophagy pathways.
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