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ePoster
A NOVEL NEUROPROTECTIVE MECHANISM OF HEXARAPHANE (6‑MSITC) DERIVED FROM WASABI
Isao Okunishi
Kinjirushi Co.,Ltd.
FENS Forum 2026 (2026)
Barcelona, Spain
Presenter and authors
Presenter
Isao Okunishi
Kinjirushi Co.,Ltd.
Abstract
Hexaraphane (HXN; 6‑methylsulfinylhexyl isothiocyanate), a bioactive compound derived from wasabi (Eutrema japonicum), has demonstrated antioxidant, anti‑inflammatory, and neuroprotective properties, partially attributed to activation of the Nrf2 pathway. However, its role in tau‑associated neurodegeneration remains insufficiently characterized. This study investigated the neuroprotective potential of HXN with a specific focus on tauopathy‑related mechanisms and translational relevance.
Mechanistic analyses integrated previously reported in vitro and in vivo experimental frameworks with complementary pharmacokinetic evaluations. Cellular and murine studies using APP/TAU transgenic models examined the effects of orally administered HXN on tau phosphorylation, phosphatase activity, neuroinflammation, synaptic plasticity, and cognitive performance. Brain exposure and regional distribution were confirmed using HPLC‑based pharmacokinetic profiling. Translational relevance was assessed through randomized human intervention studies evaluating cognitive function following daily intake of HXN‑containing wasabi‑derived supplements.
Across cellular and animal models, HXN significantly reduced pathological tau phosphorylation at disease‑relevant epitopes. This effect occurred independently of canonical tau kinases and Nrf2 signaling and was instead associated with enhanced phosphatase activity, particularly protein phosphatase 2A. Oral administration achieved measurable brain concentrations and was accompanied by suppression of neuroinflammatory markers, preservation of neuronal integrity, and improvements in synaptic and cognitive function. Consistently, human studies demonstrated significant improvements in attention, judgment, and memory, alongside reductions in neurological symptoms.
Together, these findings identify HXN as a promising brain‑penetrant compound that modulates tau‑associated pathology via phosphatase‑dependent mechanisms and support its further development as a disease‑modifying strategy for tau‑related neurodegenerative disorders.
Mechanistic analyses integrated previously reported in vitro and in vivo experimental frameworks with complementary pharmacokinetic evaluations. Cellular and murine studies using APP/TAU transgenic models examined the effects of orally administered HXN on tau phosphorylation, phosphatase activity, neuroinflammation, synaptic plasticity, and cognitive performance. Brain exposure and regional distribution were confirmed using HPLC‑based pharmacokinetic profiling. Translational relevance was assessed through randomized human intervention studies evaluating cognitive function following daily intake of HXN‑containing wasabi‑derived supplements.
Across cellular and animal models, HXN significantly reduced pathological tau phosphorylation at disease‑relevant epitopes. This effect occurred independently of canonical tau kinases and Nrf2 signaling and was instead associated with enhanced phosphatase activity, particularly protein phosphatase 2A. Oral administration achieved measurable brain concentrations and was accompanied by suppression of neuroinflammatory markers, preservation of neuronal integrity, and improvements in synaptic and cognitive function. Consistently, human studies demonstrated significant improvements in attention, judgment, and memory, alongside reductions in neurological symptoms.
Together, these findings identify HXN as a promising brain‑penetrant compound that modulates tau‑associated pathology via phosphatase‑dependent mechanisms and support its further development as a disease‑modifying strategy for tau‑related neurodegenerative disorders.