Einstien statue Hebrew University.
(photo credit: HEBREW UNIVERSITY)
A single dose of a new molecule developed by Hebrew University researchers has been shown to protect the brain – so far in mice – from inflammation, cell death and cognitive impairments that often occur after a mild traumatic brain injury (mTBI).
This injury occurs frequently in children (for example in school and road accidents) and adults, particularly among athletes and the elderly (when they fall). But because external signs or objective structural brain damage can not been seen, mTBI is an under-diagnosed injury. But it is often accompanied by long-lasting cognitive, behavioral and emotional difficulties associated with biochemical and cellular changes.
While mTBI symptoms mostly disappear within days or weeks of the injury, up to half of mTBI patients experience symptoms even a year after injury. These may include psychological symptoms, subjective cognitive impairments, and bodily complaints.
At present, there is no effective treatment for patients with mTBI.
“It is widely known that external or internal injury strongly activates the inflammatory response and leads to cell death through the mitogen-activated protein kinase (MAPK) pathways, which are involved in the cellular responses that lead to inflammation in brain cells,” said Prof. Daphne Atlas, from the biological chemistry department at the university’s Alexander Silberman Institute of Life Sciences.
“Therefore, for reversing the effects of mTBI, it is essential to calm the inflammatory pathways.”
At her Jerusalem lab, Atlas developed new molecules derived from the active site of Trx1, called thioredoxin-mimetic peptides (TXM-peptides).
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Thioredoxin is a major protein that maintains the oxidation/ reduction state of the cells. In its reduced form, it is attached to another protein (ASK1), which is released upon oxidation of Trx1 and activates a chain of enzymatic reactions that lead to inflammation.
The newly-synthesized thioredoxin- mimetic (TXM) peptides have been shown to protect cells from early death via the activation of inflammatory pathways. Comprising three or four amino acids (organic compounds that combine to form proteins), these peptides have a double activity – they mimic the antioxidant activity of Trx1 and simultaneously inhibit the activity of enzymes called MAPK within the inflammatory pathway, preventing inflammation and cell death.
“This research demonstrates the potential for TXM-peptides to significantly reduce cognitive impairment after mild traumatic brain injury,” said Atlas.
“Further studies are required to establish and examine the potential of a single dose of TXM-peptide in preventing damage if administered even one hour after brain trauma in human scenarios – for example, in chronic traumatic encephalopathy observed in US football players who received multiple concussions and other types of blows to the head,” she suggested.
“Another advantage to using peptides is in significantly reducing the risk of causing toxic effects, because they consist of amino acids, which are the natural building blocks comprising cell proteins, in contrast to the use of drugs that are not natural. So TXMCB3 and TXM-CB13 are promising treatment candidates to prevent secondary damage that affects MAPK brain function,” concluded Atlas.
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