Abstract
Background Extracellular Amyloid-b (Ab) plaques and intracellular neuro-fibrillary tangles (NFTs) of hyperphosphorylated Tau (τ) protein are considered to be the hallmarks of Alzheimer’s disease (AD) [1]. Ab is secreted due to the sequential cleavage of the amyloidb precursor protein (APP) by band gsecretases (b cleavage) [1], whereas the intracellular signalling protein glycogen synthase kinase 3 (GSK3) has been implicated to cause τhyperphosphorylation leading to the formation of NFTs [2]. It has been shown earlier that the cleavage of APP by aand gsecretases (acleavage) is enhanced by insulin through the PI3KAkt pathway [3]. GSK3 is a further downstream component of this pathway which has been shown to induce τ phosphorylation. Inhibition of GSK3 has also been shown to increase lysosomal biogenesis leading to autophagic degradation of APP [4].
Highlights
Extracellular Amyloid-b (Ab) plaques and intracellular neuro-fibrillary tangles (NFTs) of hyperphosphorylated Tau (τ) protein are considered to be the hallmarks of Alzheimer’s disease (AD) [1]
Inhibition of glycogen synthase kinase 3 (GSK3) has been shown to increase lysosomal biogenesis leading to autophagic degradation of amyloidb precursor protein (APP) [4]
Cells expressing wtAPP, bovine cGMP dependent protein kinase 1-alpha (PKG1a) and murine PKG2 were generated by lentiviral transduction and were stimulated with 200μM 8-pCPT-cGMP or/ and 1μM insulin for 15 min or 2 hrs
Summary
Extracellular Amyloid-b (Ab) plaques and intracellular neuro-fibrillary tangles (NFTs) of hyperphosphorylated Tau (τ) protein are considered to be the hallmarks of Alzheimer’s disease (AD) [1]. Ab is secreted due to the sequential cleavage of the amyloidb precursor protein (APP) by b- and g- secretases (b cleavage) [1], whereas the intracellular signalling protein glycogen synthase kinase 3 (GSK3) has been implicated to cause τ- hyperphosphorylation leading to the formation of NFTs [2]. It has been shown earlier that the cleavage of APP by a- and g- secretases (a- cleavage) is enhanced by insulin through the PI3K- Akt pathway [3]. GSK3 is a further downstream component of this pathway which has been shown to induce τ phosphorylation. Inhibition of GSK3 has been shown to increase lysosomal biogenesis leading to autophagic degradation of APP [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
