Figure 2.

Screening strategy to identify HSP70 modulators to treat Alzheimer’s disease. Molecules are screened through cell-based systems that are able to form oligomers/aggregates. These cells are HSP70(−), partially expressing HSP70, or overexpressing HSP70.

Notes: Molecules that inhibit oligomerization/aggregation are selected (A). The mechanism and specificity of selected molecules is determined by ATPase/aggregation assays. Selected molecules are screened by HSP70 ATPase assay and molecules that modulate the activity are selected (B). These molecules are used in aggregation assays and molecules that inhibit the aggregation of beta amyloid and tau are selected. Molecules that inhibit polyQ/huntingtin aggregation are eliminated due to their nonspecificity (C).

Abbreviations: A, aggregation; ATPase, adenosine triphosphatase; HSP70, heat shock protein 70; O, oligomerization.