Filbertone-Induced Nrf2 Activation Ameliorates Neuronal Damage via Increasing BDNF Expression

• Published in: Neurochemical research 2025-02, Vol.50 (1), p.44, Article 44
• Main Authors: Gong, Jeong Heon, Kim, Chu-Sook, Park, Jeongmin, Kang, Soeun, Jang, Yumi, Kim, Min-Seon, Chung, Hun Taeg, Joe, Yeonsoo, Yu, Rina
• Format: Article
• Language: English
• Subjects: Animals; Bioactive compounds; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain damage; Brain injury; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - biosynthesis; Brain-Derived Neurotrophic Factor - metabolism; Cell activation; Cell Biology; Cell Line, Tumor; Cell survival; Cell viability; Glial cell line-derived neurotrophic factor; Glial cells; Growth factors; Heme oxygenase (decyclizing); High fat diet; Humans; Hypothalamus; Male; Mice; Mice, Inbred C57BL; Movement disorders; MPP; MPTP; Nerve growth factor; Neurochemistry; Neurodegeneration; Neurodegenerative diseases; Neurology; Neuronal-glial interactions; Neurons - drug effects; Neurons - metabolism; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Neurotoxicity; Neurotoxins; NF-E2-Related Factor 2 - biosynthesis; NF-E2-Related Factor 2 - metabolism; Palmitic acid; Parkinson's disease; Pharmacology; Signal transduction; Toxins; Up-regulation
• ISSN: 0364-3190; 1573-6903; 1573-6903
• DOI: 10.1007/s11064-024-04290-x

Neurotrophic factors are endogenous proteins that promote the survival of various neuronal cells. Increasing evidence has suggested a key role for brain-derived neurotrophic factor (BDNF) in the dopaminergic neurotoxicity associated with Parkinson’s Disease (PD). This study explores the therapeutic potential of filbertone, a bioactive compound found in hazelnuts, in neurodegeneration, focusing on its effects on neurotrophic factors and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. In our study, filbertone markedly elevated the expression of neurotrophic factors, including BDNF, Glial cell line-Derived Neurotrophic Factor (GDNF), and Nerve Growth Factor (NGF), in human neuroblastoma SH-SY5Y cells, mouse astrocyte C8-D1A cells, and mouse hypothalamus mHypoE-N1 cells. Moreover, filbertone effectively countered neuroinflammation and reversed the decline in neurotrophic factors and Nrf2 activation induced by a high-fat diet (HFD) in neurodegeneration models. The neuroprotective effects of filbertone were further validated in models of neurotoxicity induced by palmitic acid (PA) and the neurotoxin MPTP/MPP + , where it was observed to counteract PA and MPTP/MPP + -induced decreases in cell viability and neuroinflammation, primarily through the activation of Nrf2 and the subsequent upregulation of BDNF and heme oxygenase-1 expression. Nrf2 deficiency negated the neuroprotective effects of filbertone in MPTP-treated mice. Consequently, our finding suggests that filbertone is a novel therapeutic agent for neurodegenerative diseases, enhancing neuronal resilience through the Nrf2 signaling pathway and upregulation of neurotrophic factors. Graphical Abstracts