Английская Википедия:BNN-20

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BNN-20, also known as 17β-spiro-(androst-5-en-17,2'-oxiran)-3β-ol, is a synthetic neurosteroid, "microneurotrophin", and analogue of the endogenous neurosteroid dehydroepiandrosterone (DHEA).[1][2] It acts as a selective, high-affinity, centrally active agonist of the TrkA, TrkB, and p75NTR, receptors for the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as for DHEA and DHEA sulfate (DHEA-S).[2][3] The drug has been suggested as a potential novel treatment for Parkinson's disease and other conditions.[2]

In 2011, the surprising discovery was made that DHEA, as well as DHEA-S, directly bind to and activate the TrkA and p75NTR with high affinity.[3] DHEA was subsequently also found to bind to the TrkB and TrkC with high affinity, though it notably activated the TrkC but not the TrkB.[4] DHEA and DHEA-S bound to these receptors with affinities that were in the low nanomolar range (around 5 nM), although the affinities were nonetheless approximately two orders of magnitude lower relative to the highly potent polypeptide neurotrophins (0.01–0.1 nM).[3][4] In any case, DHEA and DHEA-S were identified as important endogenous neurotrophic factors.[3] These findings may explain the positive association between decreased circulating DHEA levels with age and age-related neurodegenerative diseases.[2]

Subsequently, a series of spiro derivatives of DHEA that had been synthesized and assessed in 2009 as potential neuroprotective agents was re-investigated.[1][2] Of these, BNN-20 was assayed and found to directly bind to and activate the TrkA, TrkB, and p75NTR.[2] In addition, it was found to cross the blood–brain barrier and to have strong neuroprotective effects on dopaminergic neurons in vivo in a mouse model of dopaminergic neurodegeneration, which were dependent, at least in part, on activation of the TrkB.[2] Moreover, unlike DHEA, it lacked any hormonal actions.[2] As such, BNN-20 was described as a BDNF mimetic and was proposed as a potential novel treatment for Parkinson's disease and other conditions, particularly of the neurodegenerative variety, like amyotrophic lateral sclerosis.[2][5]

See also

References

Шаблон:Reflist


Шаблон:Growth factor receptor modulators

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  1. ↑ 1,0 1,1 Шаблон:Cite journal
  2. ↑ 2,0 2,1 2,2 2,3 2,4 2,5 2,6 2,7 2,8 Шаблон:Cite journal
  3. ↑ 3,0 3,1 3,2 3,3 Шаблон:Cite journal
  4. ↑ 4,0 4,1 Шаблон:Cite journal
  5. ↑ Шаблон:Cite journal
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