Neurodegenerative diseases (
NDs) are characteristic with progression of
neuron degeneration, resulting in dysfunction of cognition and mobility. Many
neurodegenerative diseases are because of
proteinopathies that results from unusual
protein accumulations and aggregations. The aggregation of misfolded
proteins like β-
amyloid, α-
synuclein, tau, and polyglutamates are hallmarked in
Alzheimer's disease (AD), which are undruggable targets, and usually do not respond to conventional small-molecule agents. Therefore, developing novel technology and strategy for reducing the levels of
protein aggregates would be critical for treatment of AD. Recently, the emerging
proteolysis targeting chimeras (PRPTACs) technology has been significantly considered for artificial and selective degradation of aberrant target
proteins. These engineered bifunctional molecules engage target
proteins to be degraded by either the cellular degradation machinery in the
ubiquitin-
proteasome system (UPS) or via the autophagy-lysosome degradation pathway. Although the application of
PROTACs technology is preferable than
oligonucleotide and
antibodies for treatment of
NDs, many limitations such as their pharmacokinetic properties, tissue distribution and cell permeabilities, still need to be corrected. Herein, we review the recent advances in
PROTACs technology with their limitation for pharmaceutical targeting of aberrant
proteins involved in
Alzheimer's diseases. We also review therapeutic potential of dysregulated signaling such as PI3K/AKT/mTOR axis for the management of AD.