abnormal interactions with many cellularproteins (10). The normal structure of the fibrils contains these dangeroussurfaces, this explaining why the soluble oligomers are much more interactivethan fibrils.  However, the fibril contributes to pathologyby both generating oligomers through fragmentation and secondary nucleation andby stably sequestering key cellular factors (12, 13). Themetastable proteins are often targeted by toxic aggregates; they are presentat the unstructured regions and low amino acid complex, can distinguish manyRNA-binding proteins (9,13). Accordingly, There is an interferes between proteinaggregation with nucleocytoplasmic RNA transport and RNA homeostasis (6,11). Many studies have proven that the proteindegradation can inhibited by the aggregates proteasome and autophagy systems (6) and can isolate chaperone components(4,13).

Proteostasis decline and symptom as a resultof interferes between aggregation with protein quality control. Aggregate is essential to determine cellviability and the life span of model organisms. Recent study by Frydman and colleagues (10),noted that there is difference between protein aggregation in the cell andaggregation in vitro which mean that cells contain complex mechanisms thatinvolve particular chaperon proteins, for instance the small heat shock proteinHsp42 (6), have been developed to minimize the toxic effects exerted by solubleoligomers (8). Actively sequester surplus and misfolded proteins into transientor stable deposits when their timely degradation fails. These mechanisms, whichinvolve specific chaperone proteins like the small heat shock protein Hsp42 (7),have apparently evolved to reduce the toxic effects exerted by solubleoligomers (13). These compartments include the insolubleprotein deposit (IPOD) which discovered in the yeast cells (12). The IPOD terminatesthe toxic amyloid and prion proteins in the cell periphery near the vacuole (8)this equivalent to the mammalian cells aggresome as a site of aggregatesequestration (11).  In the transient sequestration thecompartments are called Q-bodies and the juxtanuclear quality controlcompartment (JUNQ) (4).

The Q-bodies present immediately when proteinmisfolding, for instance, under stress they concentrate in the JUNQ in case of degradation,for instance, under stress they concentrate in the JUNQ in case of degradationif the ubiquitin proteasome system failsOther misfolded proteins is cytosolic, potentiallyrouted to an intranuclear quality control compartment (INQ) (7), which playpivotal role in degradation of cytosolic proteins and quality control (3, 11).In conclusion, the massive development thathas been made in last few years in terms of discovering the structure ofpathological protein aggregates and their mechanisms of toxicity. Together withexplaining the relationship between the effective proteostasis network and misfoldedproteins, to find way to prolong the healthy life span.