000098669 001__ 98669
000098669 005__ 20180317095317.0
000098669 037__ $$aARTICLE
000098669 245__ $$aBistability explains threshold phenomena in protein aggregation both in vitro and in vivo
000098669 269__ $$a2006
000098669 260__ $$c2006
000098669 336__ $$aJournal Articles
000098669 500__ $$a6-3 FIELD Section Title:General Biochemistry
000098669 500__ $$aDepartment of Chemical and Biological Engineering,Northwestern University,Evanston,IL,USA. FIELD URL:
000098669 500__ $$awritten in English.
000098669 520__ $$aNeurodegenerative disease can originate from the misfolding and aggregation of proteins, such as Amyloid-beta, SOD1, or Huntingtin. Fortunately, all cells possess protein quality control machinery that sequesters misfolded proteins, either refolding or degrading them, before they can self-assoc. into proteotoxic oligomers and aggregates. This activity is largely performed by the stress response chaperones (i.e., Hsp70). However, the expression level of mol. chaperones varies widely among cell types. To understand the potential consequence of this variation, we studied the process of protein aggregation in the presence of mol. chaperones using math. modeling. We demonstrate that protein aggregation, in the presence of mol. chaperones, is a bistable process. Bistability in protein aggregation offers an explanation for threshold transitions to high aggregate concn., which are obsd. both in vitro and in vivo. Addnl., we show that slight variations in chaperone concn., due to natural fluctuations, have important consequences in a bistable system for the onset of protein aggregation. Therefore, our results offer a possible theor. explanation for neuronal vulnerability obsd. in vivo and the onset of neurodegenerative phenotypes in neurons lacking an effective heat-shock response. [on SciFinder (R)]
000098669 6531_ $$aprotein aggregation model bistability threshold chaperone
000098669 700__ $$aRieger, Theodore R.
000098669 700__ $$aMorimoto, Richard I.
000098669 700__ $$0240657$$aHatzimanikatis, Vassily$$g174688
000098669 773__ $$j90$$k3$$q886-895$$tBiophysical Journal
000098669 8564_ $$s229520$$uhttps://infoscience.epfl.ch/record/98669/files/vh-2006-4.pdf$$zn/a
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000098669 909C0 $$0252131$$pLCSB$$xU11422
000098669 937__ $$aLCSB-ARTICLE-2006-003
000098669 970__ $$a0000000005/LCSB
000098669 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000098669 980__ $$aARTICLE