Reducing the levels of toxic protein aggregates has become a focus of therapy 
for disorders like Alzheimer's and Parkinson's diseases, as well as for the 
general deterioration of cells and tissues during aging. One approach has been 
an attempt to influence the production or activity of a class of reparative 
chaperones called heat shock proteins (HSPs), of which HSP70 is a promising 
candidate. Manipulation of HSP70 expression results in disposal of misfolded 
protein aggregates that accumulate in aging and disease models. Recently, HSP70 
has been shown to bind specifically to an amino-terminal sequence of a human 
diffusible survival evasion peptide (DSEP), dermcidin. This sequence includes 
CHEC-9, an orally available anti-inflammatory and cell survival peptide. In the 
present study, we found that the CHEC-9 peptide also binds HSP70 in the cytosol 
of the cerebral cortex after oral delivery in normal rats. Western analysis of 
non-heat-denatured, unreduced samples suggested that peptide treatment increased 
the level of active HSP70 monomers from the pool of chaperone oligomers, a 
process that may be stimulated by potentiation of the chaperone's adenosine 
triphosphatase (ATPase). In these samples, a small but consistent gel shift was 
observed for glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a multifunctional 
protein whose aggregation is influenced by HSP70. CHEC-9 treatment of an in 
vitro model of α-synuclein aggregation also results in HSP70-dependent 
dissolution of these aggregates. HSP70 oligomer-monomer equilibrium and its 
potential to control protein aggregate disease warrant increased experimental 
attention, especially if a peptide fragment of an endogenous human protein can 
influence the process.