A wide range of neurodegenerative diseases are characterized by the deposition of multiple protein aggregates.
For example, cells stressed with heat respond by forming multiple protein aggregates (referred to as peripheral aggregates, stress foci, Q-bodies, or CytoQ) at the surface of the ER (Specht et al., 2011; Spokoini et al., 2012; Escusa-Toret et al., 2013; Miller et al., 2015; Zhou et al., 2014; Wallace et al., 2015).
Many neurodegenerative diseases, including PD and LBD, are marked by multiple different protein aggregates.
These results demonstrate that the formation of multiple protein layers is localized in specific nanometric structures; in fact, part of the surface pores is filled by proteins that aggregate inside the pores.
Using the pan-desmin antibody, muscle tissue from young HOM animals already displayed a highly abnormal staining pattern with fibers containing multiple subsarcolemmal and sarcoplasmic desmin-positive protein aggregates as well as multiple fibers with virtually no sarcoplasmic desmin staining.
Motor neuron death in ALS is a complex process, and may involve multiple pathways including formation of protein aggregates, axonal transport defects, oxidative damage, mitochondrial defects, and alterations in calcium homeostasis [6].
Direct therapeutic targeting of aggregates is challenging because (1) the prefibrillar protein aggregates can have multiple structural conformations, (2) not all aggregates will be toxic, and (3) the different toxic species may be toxic through different mechanisms.
It has been recently discovered that protein aggregates, as they form, sequester multiple pre-existent and newly synthesized proteins that have essential cellular functions and thus are critical for cell survival (Olzscha et al., 2011).
However, it has been recently discovered that protein aggregates, as they form, sequester multiple pre-existent and newly synthesized proteins that have essential cellular functions and are critical for cell survival (Olzscha et al., 2011).
In this model, nuclear bodies are essentially dynamic protein aggregates which form as a consequence of multiple, transient interactions amongst a large number of proteins.
