Effective neurofibromatosis therapeutics blocking the oncogenic kinase PAK1.
@article{Maruta2011EffectiveNT, title={Effective neurofibromatosis therapeutics blocking the oncogenic kinase PAK1.}, author={Hiroshi Maruta}, journal={Drug discoveries \& therapeutics}, year={2011}, volume={5 6}, pages={ 266-78 } }
Neurofibromatosis (NF) is a family of genetic diseases which are caused by dysfunction of either NF1 gene or NF2 gene. One in 3,000 people suffer from this tumor-carrying NF. NF1 gene product is a RAS GTPase activating protein (GAP) of 2,818 amino acids, which normally attenuates the GTP-dependent signal transducing activity of the G protein RAS. Dysfunction of this GAP leads to the abnormal activation of RAS, and eventually an oncogenic kinase called PAK1 as well. NF2 gene product is ''Merlin…
Figures and Tables from this paper
21 Citations
The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?
- Biology, MedicineFrontiers in Cell and Developmental Biology
- 2021
The structure, function, alteration, and molecular mechanisms of PAKs that are involved in the pathogenic and oncogenic effects, as well as PAK inhibitors, which may be developed and deployed in cancer therapy, anti-viral infection, and other diseases are discussed.
Herbal Therapeutics that Block the Oncogenic Kinase PAK1: A Practical Approach towards PAK1‐dependent Diseases and Longevity
- Biology, MedicinePhytotherapy research : PTR
- 2014
Mainly pathological phenotypes of hyper‐activated PAK1 are outlined and a list of herbal therapeutics that blockPAK1, but cause no side (harmful) effect on healthy people or animals are outlined.
PAKs in Human Cancer Progression: From Inception to Cancer Therapeutic to Future Oncobiology.
- BiologyAdvances in cancer research
- 2016
A computational approach to explore and identify potential herbal inhibitors for the p21-activated kinase 1 (PAK1)
- Biology, ChemistryJournal of biomolecular structure & dynamics
- 2019
The results conform to the previous experimental evidences, and therefore, NA from Okinawa propolis could be a promising inhibitor for treating PAK1-dependent illnesses.
PAK1-deficiency/down-regulation reduces brood size, activates HSP16.2 gene and extends lifespan in Caenorhabditis elegans.
- BiologyDrug discoveries & therapeutics
- 2013
It is 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, which support the "trade-off" theory on reproduction versus lifespan.
Tracing PAKs from GI inflammation to cancer
- BiologyGut
- 2014
The importance of altered PAK activation within GI inflammation is highlighted, its effect on oncogenic signalling is emphasised and PAKs as therapeutic targets of chemoprevention are discussed.
Therapeutic potential of Pak1 inhibition for pain associated with cutaneous burn injury
- Biology, MedicineMolecular pain
- 2018
A longitudinal study to address the hypothesis that inhibition of the downstream effector of Rac1, Pak1, will improve pain outcome following a second-degree burn injury identifies Pak1 signaling as a potential molecular target for therapeutic intervention in traumatic burn-induced neuropathic pain.
Fast and Robust Next-Generation Sequencing Technique Using Ion Torrent Personal Genome Machine for the Screening of Neurofibromatosis Type 1 (NF1) Gene
- BiologyJournal of Molecular Neuroscience
- 2014
In this examination, the aim was to work out a method to use the high-throughput NGS machine, Ion Torrent PGM, in diagnostic settings for neurofibromatosis type 1, and could reveal 21 distinct variations in NF1 gene in seven patients.
References
SHOWING 1-10 OF 114 REFERENCES
Signal therapy of NF1-deficient tumor xenograft in mice by the anti-PAK1 drug FK228
- Biology, MedicineCancer biology & therapy
- 2005
It is demonstrated that the anti-PAK1 drug FK228 completely blocks the growth of both NF1-deficient and NF2-deficent cancer cells in vitro and causes the complete regression of an NF1 -deficient human malignant peripheral nerve sheath tumor (MPNST) xenograft in nude mice.
Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice
- Biology, PsychologyProceedings of the National Academy of Sciences
- 2007
The results demonstrate the genetic rescue of phenotypes in a FXS mouse model and suggest that the PAK signaling pathway, including the catalytic activity of PAK, is a novel intervention site for development of an FXS and autism therapy.
Sichuan pepper extracts block the PAK1/Cyclin D1 pathway and the growth of NF1-deficient cancer xenograft in mice
- BiologyCancer biology & therapy
- 2006
The first evidence that extracts of Chinese/ Japanese peppercorns, from the plant Zanthoxylum piperitum called “Hua Jiao”/ “Sansho”, block selectively the key kinase PAK1, leading to the down-regulation of cyclin D1 is provided.
Effects of Rapamycin in the Eker Rat Model of Tuberous Sclerosis Complex
- Medicine, BiologyPediatric Research
- 2005
It is concluded thatRapamycin-sensitive mTOR activity was critical to tumor progression in the Eker rat model, but rapamycin is unlikely to eradicate all disease as a result of the development of drug resistance.
p21-activated Kinase-aberrant Activation and Translocation in Alzheimer Disease Pathogenesis*
- BiologyJournal of Biological Chemistry
- 2008
It is demonstrated that PAK is aberrantly activated and translocated from cytosol to membrane in Alzheimer disease brain and in 22-month-old Tg2576 transgenic mice with Alzheimer disease, which implicate aberrant PAK in Aβ oligomer-induced signaling and synaptic deficits in dementia.
Signal therapy of breast cancers by the HDAC inhibitor FK228 that blocks the activation of PAK1 and abrogates the tamoxifen-resistance
- BiologyCancer biology & therapy
- 2005
Evidence suggesting that breast cancers require PAK1 for their estrogen-dependent growth is provided, suggesting that FK228 and other anti-PAK1 drugs would be useful for the treatment of breast cancers which become resistant to currently used estrogen antagonists such as tamoxifen.
p21-activated kinase 1: an emerging therapeutic target.
- BiologyCancer treatment and research
- 2004
Emerging studies unraveling the novel roles of Pak1 signaling and the possible clinical potential of targeting Pak1 will continue to stimulate efforts to develop Pak1 inhibitors or blockers.
Regression of subependymal giant cell astrocytomas with RAD001 (Everolimus) in tuberous sclerosis complex
- Medicine, PsychologyChild's Nervous System
- 2010
Oral RAD001 demonstrated preliminary encouraging results as treatment of astrocytomas associated with TSC, supported by the Novartis announcement of the phase II study of RAD001 for SEGAs, which was not published yet.
The pre-GAP-related domain of neurofibromin regulates cell migration through the LIM kinase/cofilin pathway
- BiologyMolecular and Cellular Neuroscience
- 2009
Signal therapy for RAS-induced cancers in combination of AG 879 and PP1, specific inhibitors for ErbB2 and Src family kinases, that block PAK activation.
- BiologyCancer journal
- 2001
It is demonstrated that the PAK-PIX interaction is essential for v-Ha-RAS-induced malignant transformation, and a new avenue for the treatment of RAS-associated cancers by a combination of inhibitors specific for ERbB, Src, or PAK family kinases is suggested.