Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is an increasing evidence that the oncogenic kinase PAK1 is responsible not only for malignant transformation, but also for several other diseases such as inflammatory diseases (asthma and arthritis), infectious diseases including malaria, AIDS, and flu, as well as a series of neuronal diseases/disorders (neurofibromatosis, tuberous sclerosis, Alzheimer's diseases, Huntington's disease, epilepsy, depression, learning deficit, etc.) which often cause premature death. Interestingly, a few natural PAK1-blockers such as curcumin, caffeic acid (CA) and rosmarinic acid (RA) extend the lifespan of the nematode Caenorhabditis elegans or fruit flies. Here, to explore the possibility that C. elegans could provide us with a quick and inexpensive in vivo screening system for a series of more potent but safe (non-toxic) PAK1-blocking therapeutics, we examined the effects of PAK1-deficiency or down-regulation on a few selected functions of this worm, including reproduction, expression of HSP16.2 gene, and lifespan. In short, we found that PAK1 promotes reproduction, whereas it inactivates HSP16.2 gene and shortens lifespan, as do PI-3 kinase (AGE-1), TOR, and insulin-like signalling /ILS (Daf-2) in this worm. These findings not only support the "trade-off" theory on reproduction versus lifespan, but also suggest the possibility that the reduced reproduction (or HSP16.2 gene activation) of this worm could be used as the first indicator of extended lifespan for a quick in vivo screening for PAK1-blockers.
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PMID:PAK1-deficiency/down-regulation reduces brood size, activates HSP16.2 gene and extends lifespan in Caenorhabditis elegans. 2352 41

To prepare for future resistance, new methods are being explored for novel treatment of malaria. The current work uses high performance docking methods to model different substrates binding into the active sites of varying Homo sapien and Plasmodium peptidyl-prolyl cis/trans isomerase enzymes and compares their subsequent docking scores. This approach has shown that the substrates ILS-920 and WYE-592 will bind less-favourably with hFKBP12 and PfFKBP35 compared to a competing substrate rapamycin; however, the binding appears to be more favourable in PvFKBP35. This could suggest a possible target for inhibition of the Plasmodium vivax parasite.
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PMID:Molecular docking study of macrocycles as Fk506-binding protein inhibitors. 2597 4