T-2 Toxin Neurotoxicity: Molecular Mechanisms and Emerging Chemoprotective Strategies

Mycotoxins can contaminate food and raw food materials and are a threat to animal and human health. T-2 toxin is the most toxic secondary metabolite mainly produced by Fusarium species among trichothecenes. T-2 toxin exposure can induce multiple toxic effects, including hepatotoxicity, nephrotoxicity, immunotoxicity, gastrointestinal toxicity, and reproductive toxicity. Recent studies have reported that T-2 toxin can cross the blood–brain barrier and trigger neurotoxicity. In this review, we summarized the neurotoxic effects caused by T-2 toxin exposure and the underlying molecular mechanisms. Additionally, effective neuroprotective agents, potential clinical applications, and future prospects are discussed. The current studies revealed that the molecular mechanisms of T-2 toxin-induced neurotoxicity involve oxidative stress, mitochondrial dysfunction, neuroinflammation, autophagy, ferroptosis and cell apoptosis. Several signaling pathways, including NFE2L2, NRF-2, PGC-1, p53, BTG2, AKNA, MAPK, Akt, mTOR, HMGB1, HIF-1, CREB, and NF-κB, are involved. Additionally, it was reported that several antioxidants, small inhibitors and nature products, such as daucosterol, betulinic acid, AHN 1-055 hydrochloride, dimethyl fumarate and minocycline supplementations, can partly ameliorate these harmful effects. This review provides valuable insights into the underlying mechanisms of T-2 toxin-induced neurotoxicity and novel effective detoxification strategies.