Peptides as Potential Therapeutics for Alzheimer's Disease

Intracellular synthesis, folding, trafficking and degradation of proteins are controlled and integrated by proteostasis. The frequency of protein misfolding disorders in the human population, e.g., in Alzheimer's disease (AD), is increasing due to the aging population. AD treatment options are limited to symptomatic interventions that at best slow-down disease progression. The key biochemical change in AD is the excessive accumulation of per-se non-toxic and soluble amyloid peptides (A beta (1-37/44), in the intracellular and extracellular space, that alters proteostasis and triggers A beta modification (e.g., by reactive oxygen species (ROS)) into toxic intermediate, misfolded soluble A beta peptides, A beta dimers and A beta oligomers. The toxic intermediate A beta products aggregate into progressively less toxic and less soluble protofibrils, fibrils and senile plaques. This review focuses on peptides that inhibit toxic A beta oligomerization, A beta aggregation into fibrils, or stabilize A beta peptides in non-toxic oligomers, and discusses their potential for AD treatment.