Words similar to misfolded
Example sentences for: misfolded
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These large spots were reminiscent of recently described aggresomes, accumulations of misfolded protein that are being targeted for proteasome-dependent degradation [ 17 18 ] . This observation suggested the possibility that intracellular localization of sα i2 may reflect targeting to a proteasome-dependent degradative pathway.
However, there are many case reports describing patients with progressive neurodegenerative disorders of unknown etiology, collectively referred to as neuronal intranuclear inclusion disease [ 77 ] . While these may consist mainly of unidentified poly-Gln or poly-Ala disorders, the present study raises the possibility that some forms of this disease may arise through unexpected mechanisms, perhaps involving mutations in Rab24 or other poorly characterized members of the Rab GTPase family that mediate trafficking of misfolded proteins within autophagosomes and lysosomes.
They can act as anti-oxidants (to prevent damage from oxygen radicals), as chaperones (to prevent misfolded proteins from forming aggregates), as antimicrobials (to protect against bacteria and fungi), and as metabolic agents.
Indeed, a similar explanation has been invoked to explain the presence of Hsp70 and ubiquitin in nuclear aggregates observed in cells expressing abnormal gene products with poly-Gln tracts, such as huntingtin [ 54 ] and ataxin-1 [ 59 ] . Based on reports that overexpression of chaperones [ 59 62 ] or a dominant-negative form of the ubiquitin-conjugating enzyme [ 63 ] can suppress the formation of poly-Gln protein aggregates, Kaytor and Warren [ 58 ] proposed a three-stage model wherein (i) molecular chaperones initially associate with the misfolded protein, (ii) failure to diminish the pool of misfolded protein leads to aggregation and ubiquitination and (iii) inefficient degradation of the aggregate by the proteasome is manifested by the accumulation of inclusion bodies.
Interestingly, Rab24 has been implicated as a possible mediator of autophagy in a recent study where wild-type GFP-Rab24 was observed to accumulate on large autophagic vacuoles in cells subjected to amino acid starvation [ 43 ] . Thus, if Rab24(D123I) functions as a true dominant suppressor of endogenous Rab24, the inclusions observed in the present study may consist of misfolded endogenous proteins that cannot be degraded because basal activity of the autophagosome-lysosome pathway is blocked.
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