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<p>Parkinson’s disease is an progressive neurodegenerative condition whose pathology manifests as the selective destruction of dopaminergic (dopamine-producing) neurons in the substantia nigra, which in turn builds up into a&#xa0;spectrum of motor and non-motor impairment. Its etiopathogenesis is indeed multidimensional, which also includes oxidative damage, mitochondrial injury, chronic neuroinflammatory responses, and pathogenic aggregations of α-synuclein; traditionally, the role of the current therapeutic regimens has been limited to the palliative treatment of symptoms and does not prevent disease progression. Recently, the flavonol fisetin (3,3′,4′,7-tetrahydroxyflavone), which is available in an array of foods, has drawn the scientific interest as a&#xa0;potential neuroprotective factor due to the presence of strong antioxidant, anti-inflammatory, and neurotrophic capabilities. Computational docking experiments indicate that fisetin can form high-affinity interactions with multiple Parkinson-relevant targets: the D2&#xa0;dopamine receptor (free energy = −10.2 kcal/mol), tumor necrosis factor alpha (−9.0 kcal/mol), nuclear factor kappaB (−6.9 kcal/mol) and the 5‑HT1A (−8.5 kcal/mol). Such interactions imply that fisetin can regulate dopaminergic and serotonergic signaling pathways, at the same time suppressing the neuroinflammatory responses. These hypotheses are supported by empirical studies in-vitro and in-vivo; fisetin increases the viability of PC12 cells, decreases the α‑synuclein burden, recovers the levels of antioxidative enzymes (SOD, CAT, and GPx), and lowers the oxidative biomarkers of malondialdehyde and nitric oxide. This review attempts to critically evaluate the multiplex neuroprotective profile of fisetin in Parkinson’s disease, integrating molecular docking.</p>

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Fisetin as a neuroprotective agent: Docking-based modulation of dopaminergic and inflammatory pathways in Parkinson’s disease

  • 期刊论文

  • 发表日期：

    2024年1月1日

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  • Ayaz Yousaf,
  • Anish Singh,
  • Diksha Dalal

摘要

Parkinson’s disease is an progressive neurodegenerative condition whose pathology manifests as the selective destruction of dopaminergic (dopamine-producing) neurons in the substantia nigra, which in turn builds up into a spectrum of motor and non-motor impairment. Its etiopathogenesis is indeed multidimensional, which also includes oxidative damage, mitochondrial injury, chronic neuroinflammatory responses, and pathogenic aggregations of α-synuclein; traditionally, the role of the current therapeutic regimens has been limited to the palliative treatment of symptoms and does not prevent disease progression. Recently, the flavonol fisetin (3,3′,4′,7-tetrahydroxyflavone), which is available in an array of foods, has drawn the scientific interest as a potential neuroprotective factor due to the presence of strong antioxidant, anti-inflammatory, and neurotrophic capabilities. Computational docking experiments indicate that fisetin can form high-affinity interactions with multiple Parkinson-relevant targets: the D2 dopamine receptor (free energy = −10.2 kcal/mol), tumor necrosis factor alpha (−9.0 kcal/mol), nuclear factor kappaB (−6.9 kcal/mol) and the 5‑HT1A (−8.5 kcal/mol). Such interactions imply that fisetin can regulate dopaminergic and serotonergic signaling pathways, at the same time suppressing the neuroinflammatory responses. These hypotheses are supported by empirical studies in-vitro and in-vivo; fisetin increases the viability of PC12 cells, decreases the α‑synuclein burden, recovers the levels of antioxidative enzymes (SOD, CAT, and GPx), and lowers the oxidative biomarkers of malondialdehyde and nitric oxide. This review attempts to critically evaluate the multiplex neuroprotective profile of fisetin in Parkinson’s disease, integrating molecular docking.