Reduced RAN Expression and Disrupted Transport between Cytoplasm and Nucleus; A Key Event in Alzheimer’s Disease PathophysiologyReportar como inadecuado




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Transcription of DNA is essential for cell maintenance and survival; inappropriate localization of proteins that are involved in transcription would be catastrophic. In Alzheimer’s disease brains, and in vitro studies, we have found qualitative and quantitative deficits in transport into the nucleus of DNA methyltransferase 1 DNMT1 and RNA polymerase II RNA pol II, accompanied by their abnormal sequestration in the cytoplasm. RAN RAs-related Nuclear protein knockdown, by siRNA and oligomeric Aβ42 treatment in neurons, replicate human data which indicate that transport disruption in AD may be mechanistically linked to reduced expression of RAN, a pivotal molecule in nucleocytoplasmic transport. In vitro studies also indicate a significant role for oligomeric Aβ42 in the observed phenomena. We propose a model in which reduced transcription regulators in the nucleus and their increased presence in the cytoplasm may lead to many of the cellular manifestations of Alzheimer’s disease.



Autor: Diego Mastroeni, Leonidas Chouliaras, Andrew Grover, Winnie S. Liang, Kevin Hauns, Joseph Rogers, Paul D. Coleman

Fuente: http://plos.srce.hr/



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