ClpX is a member of the Clp/Hsp100 family of ATP-dependent chaperones and partners with ClpP, a compartmentalized protease, to degrade protein substrates bearing specific recognition signals. ClpX targets specific proteins for degradation directly or with substrate-specific adaptor proteins. Native substrates of ClpXP include proteins that form large oligomeric assemblies, such as MuA, FtsZ, and Dps in Escherichia coli. To remodel large oligomeric substrates, ClpX utilizes multivalent targeting strategies and discriminates between assembled and unassembled substrate conformations. Although ClpX and ClpP are known to associate with protein aggregates in E. coli, a potential role for ClpXP in disaggregation remains poorly characterized. Here, we discuss strategies utilized by ClpX to recognize native and non-native protein aggregates and the mechanisms by which ClpX alone, and with ClpP, remodels the conformations of various aggregates. We show that ClpX promotes the disassembly and reactivation of aggregated Gfp-ssrA through specific substrate remodeling. In the presence of ClpP, ClpX promotes disassembly and degradation of aggregated substrates bearing specific ClpX recognition signals, including heat-aggregated Gfp-ssrA, as well as polymeric and heat-aggregated FtsZ, which is a native ClpXP substrate in E. coli. Finally, we show that ClpX is present in insoluble aggregates and prevents the accumulation of thermal FtsZ aggregates in vivo, suggesting that ClpXP participates in the management of aggregates bearing ClpX recognition signals.

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The purpose of the present study was to conduct a systematic review of the literature, adhering to PRISMA guidelines, regarding evidence of neuroplasticity in children and adolescents in response to cognitive or sensory-motor interventions. Twenty-eight studies employing seven different types of neuroimaging techniques were included in the review. Findings revealed that significant variability existed across the 28 studies with regard to the clinical populations examined, type of interventions employed, neuroimaging methods, and the type of neuroimaging data included in the studies. Overall, results supported that experience-dependent interventions were associated with neuroplastic changes among children and adolescents in both neurotypical and clinical populations. However, it remains unclear whether these molecular neuroplastic changes, including the degree and direction of those differences, were the direct result of the intervention. Although the findings are encouraging, methodological limitations of the studies limit clinical utility of the results. Future studies are warranted that rigorously define the construct of neuroplasticity, establish consistent protocols across measurement techniques, and have adequate statistical power. Lastly, studies are needed to identify the functional and structural neuroplastic mechanisms that correspond with changes in cognition and behavior in child and adolescent samples.

Protein misfolding is a hallmark of several neurodegenerative diseases, leading to the formation of non‐native amyloid deposits that correlate with disease progression. Alzheimer's disease, Parkinson's disease, Huntington's disease, and Creutzfeldt‐Jakob disease are examples of neurodegenerative diseases that share the neuropathological feature of amyloid deposits. Molecular chaperones are a class of proteins that catalyze the folding or activation of nascent proteins, the refolding and reactivation of misfolded proteins, and the disaggregation of protein aggregates. Several proteins, including the ATP‐dependent chaperone Hsp104, have been shown to disassemble amyloid fibers in vitro and in vivo. In the Saccharomyces cerevisiae model for prion propagation and inheritance, [PSI+], reduced amyloid burden correlates with the development of pigmentation attributable to an impaired adenine biosynthesis pathway. This colorimetric conversion assay has been extensively utilized to qualitatively compare the ability of chaperones to cure the cells of amyloid. We developed a quantitative assay to compare the pigmentation in yeast cell lysates, which allows for screening of mutants partially defective for amyloid curing. Using this assay, we compared the extent of amyloid clearance resulting from expression of several chaperones, including Hsp104 wild type and mutant proteins. These studies provide a platform to compare the effectiveness of different chaperone systems and partial loss of function mutants for reducing amyloid burden.

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