From the Research
Amanitin, a toxin found in certain mushrooms such as death caps (Amanita phalloides), primarily inhibits RNA polymerase II, an enzyme essential for transcribing DNA into messenger RNA in eukaryotic cells, a critical step in protein synthesis. This inhibition rapidly affects cells with high protein turnover rates, such as those in the liver and kidneys, leading to cell death. The liver is particularly vulnerable because it attempts to detoxify the compound, concentrating the poison in hepatocytes. This mechanism explains why amanitin poisoning causes severe liver damage, often leading to liver failure within days of mushroom ingestion. According to a study published in 2015 1, amatoxins, especially α-amanitin, are the main responsible for the toxic effects in humans, and it is recognized that α-amanitin inhibits RNA polymerase II, causing protein deficit and ultimately cell death. Another study published in 2024 2 also confirms that α-amanitin irreversibly and potently inhibits eukaryotic RNA polymerase II (RNAP II), leading to cell death.
The toxin is extremely potent, with even small amounts capable of causing fatal damage. Some studies have explored the potential use of α-amanitin as a payload in antibody-drug conjugates (ADCs) for cancer therapy, showing promising therapeutic effects and good tolerance in primates 2. However, the current challenges include the not fully understood toxicological mechanism of α-amanitin and the lack of clinical studies to evaluate the therapeutic efficacy of ADCs developed based on α-amanitin.
In terms of treatment, a study published in 2015 3 found that polymyxin B has an effective antidotal effect against α-amanitin poisoning, potentially binding to RNAP II in the same interface as α-amanitin and preventing the toxin from binding to RNAP II. This study suggests that polymyxin B could be used as an antidote for A. phalloides poisoning in humans.
Key points to consider:
- Amanitin inhibits RNA polymerase II, leading to cell death
- The liver and kidneys are particularly vulnerable to amanitin poisoning
- Polymyxin B may be an effective antidote against α-amanitin poisoning
- α-Amanitin has potential as a payload in ADCs for cancer therapy, but further research is needed to fully understand its toxicological mechanism and therapeutic efficacy.