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2016年3月1日 星期二

Neurodegenerative Disorder

Abnova Mar E-Newsletter
New Discoveries on Neurodegenerative Disorder
  • Strong evidence has emerged to implicate disturbed mitochondrial fusion and fission as central pathological components underpinning a number of neurodegenerative disorders. Imbalances in mitochondrial fusion and fission affects respiratory chain function, mitochondrial quality control (mitophagy), and programmed cell death. The same cellular processes are also implicated in more-common complex neurodegenerative disorders, such as Alzheimer disease and Parkinson disease. This indicates a common pathological thread and a close relationship among mitochondrial structure, function and localization. (Nature Reviews Neurology, 2015)
  • A mitochondrial fission arrest phenotype may cause elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Findings suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. The findings on this research brings new attention to the major role of mitochondrial dynamics in regulating neuronal survival. (Scientific Reports, 2016)
  • Mutations in Parkin and PINK1 cause an inherited early-onset form of Parkinson's disease. The two proteins function together in a mitochondrial quality control pathway. Here, a binding switch between phospho-ubiquitin (pUb) and the ubiquitin-like domain (Ubl) of Parkin was found to play a key role in the release of auto-inhibited ubiquitin ligase activity of Parkin. (The EMBO J, 2015)
Neurodegenerative Disorders
Alzheimer's Disease Abs Huntington's Disease Abs Parkinson's Disease Abs

Mitochondria Implicated Neurodegenerative Disorder Pathways
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References
Florence Burté, et.al. (2015). Nature Review Neurology. DOI: 10.1038/nrneurol.2014.228
Liang Zhang, et. al. (2016) Nature Scientific Reports, DOI: 10.1038/srep18725
Véronique Sauvé, et. al. (2015) The EMBO Journal. DOI: 10.15252/embj.201592237

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RNAi Regulations

New Discoveries through RNA interference
  • RNA interference has been developed as methods to evaluate IKK-NF-κB pathway in lung cancer through the influence of IKKα or IKKβ inhibition on NF-κB transcriptional activity and the effects of siRNA-mediated IKK inhibition on cancer proliferation. (Methods in Molecular Biology,2015)
  • High-throughput RNAi kinome screen targeting 720 kinases has identified PDK1 as a factor mediating resistance to CDK4/6 inhibition; thus, it can be a potential drug target in combination with CDK4/6 inhibitor LEE011 to treat ER+ breast cancer. (Cancer Research,2015)
  • Through RNA interference screen, genes, such as TACR1, were identified as factors involved in stress response of mammalian cells and further provides new approaches to reduce the mortality caused by renal ischemia. (Cell Death & Differentiation,2015)

RNAi Pathways
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  Antibody Validated Chimera Pre-design Chimera
Angiogenesis 2 40
Apoptosis 14 470
Binding 65 2671
Cell Ad/ Junc/ Cytoskeleton 10 535
Cell Cycle 30 704
Cytokine N/A 56
Enzyme 52 793
Membrane 40 2778
Metabolism 13 333
Neurobiology 3 151
Plasma/ Serum 25 860
Signal Transduction 13 623
Stem Cell 10 239
Transcriptions 45 957
Ubiquitin 6 441
Others 45 3200

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References
Bassères, D.S., et.al. (2015). Methods in Molecular Biology. DOI:10.1007/978-1-4939-2422-6_27
Jansen, V.M., et.al. (2015). Cancer Research. DOI:10.1158/1538-7445.AM2015-2844
Zynda, E.R.., et. al. (2015). Cell Death & Differentiation. DOI:10.1038/cdd.2015.128

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