Abstract
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 (Aβ(1-37/44), in the intracellular and extracellular space, that alters proteostasis and triggers Aβ modification (e.g., by reactive oxygen species (ROS)) into toxic intermediate, misfolded soluble Aβ peptides, Aβ dimers and Aβ oligomers. The toxic intermediate Aβ products aggregate into progressively less toxic and less soluble protofibrils, fibrils and senile plaques. This review focuses on peptides that inhibit toxic Aβ oligomerization, Aβ aggregation into fibrils, or stabilize Aβ peptides in non-toxic oligomers, and discusses their potential for AD treatment.
Highlights
Intracellular synthesis, folding, trafficking and degradation of proteins are controlled and integrated by proteostasis
This review focuses on peptides that inhibit toxic amyloid β (Aβ) oligomerization, Aβ aggregation into fibrils, or stabilize Aβ peptides in non-toxic oligomers, and discusses their potential for Alzheimer’s disease (AD) treatment
Amyloid Precursor Protein (APP) is preferentially processed by the non-amyloidogenic pathway and increased amyloid β-peptides (Aβps) production correlates with decreased sAPPα levels [31,32,33,34]
Summary
The increase in life expectancy is accompanied with an increased number of patients suffering from Alzheimer’s disease (AD). AD is the most common cause of dementia, with a prevalence that increases with age to about 50%. The worldwide number of patients with AD is projected to increase to more than 140 million in 2050 [2].The total estimated worldwide cost of dementia in 2015 was US $818 billion, will reach US $1 trillion in 2018 and US $2 trillion by 2030. The true number of patients and the associated cost of dementia are likely to be considerably higher, since a huge majority of people with dementia have not received a diagnosis, have not been registered, and are unable to access care and treatment [3]
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