More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration

ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain.

“ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain.”

Reelin-mediated signaling through LRP8/APOER2 and very-low-density-lipoprotein receptor is crucial to synaptic plasticity.

“reelin-mediated signaling through LRP8/APOER2 and very-low-density-lipoprotein receptor is crucial to synaptic plasticity (Lane-Donovan et al., 2014).”

Astrocyte-derived ApoE is important for cholesterol transport through ApoE-containing 'HDL-like' particles, which play an important role in synaptic development and maintenance.

“Astrocyte-derived ApoE is important for cholesterol transport through ApoE-containing “HDL-like” particles, which play an important role in synaptic development and maintenance [1, 4, 5].”

Reelin signaling through the Dab1/PI3K/Akt pathway reduces tau phosphorylation by inhibiting GSK-3β, which would stabilize microtubules and help maintain synaptic stability.

“At the same time, Reelin signaling through the Dab1/PI3K/Akt pathway reduces this phosphorylation by inhibiting glycogen synthase kinase-3␤ (GSK-3␤) (reviewed in Ref. 31) (Figs.1B and 3F), which would stabilize microtubules and help maintain synaptic stability.”

Oligomeric Aβ particles suppress LTP and enhance LTD through interactions with synaptic proteins such as mGluRs and potentially α7-nAChR.

“Oligomeric A␤ particles suppress LTP and enhance long-term depression (LTD) through interactions with synaptic proteins (and reviewed in Refs.31 and 55), such as metabotropic glutamate receptors (mGluRs) as well as potentially the Ca 2ϩ -permeable ␣7-nicotinic acetylcholine receptor (␣7-nAChR) (reviewed in Refs.56 and 57).”

The amyloidogenic fate of APP is determined by the initial secretase cleavage step; non-amyloidogenic cleavage is mediated by α-secretases, whereas amyloidogenic processing starts primarily in endosomal compartments by β-secretase cleavage.

“The amyloidogenic fate of APP is determined by the initial secretase cleavage step.Non-amyloidogenic cleavage of APP is mediated by extracellular ␣-secretases, whereas amyloidogenic processing starts primarily in endosomal compartments by ␤-secretase cleavage (reviewed in Refs.31 and 50).”

Initial studies in cell lines found that endocytosed particles of lipidated ApoE4 remained in endosomes longer.

“Initial studies in cell lines found that endocytosed particles of lipidated ApoE4 remained in endosomes longer (reviewed in Ref. 31).”

Reduced Reelin expression in HRM mice exacerbates the accumulation of both Aβ and phosphorylated tau, whose production is inhibited by Reelin signaling.

“Reduced Reelin expression in HRM mice exacerbates the accumulation of both A␤ and phosphorylated tau (94), whose production is inhibited by Reelin signaling (Ref.76 and reviewed in Ref. 31).”

Reelin signaling is implicated in protecting against pathological effects of ApoE4.

“In addition to protecting against A␤and tau-related AD pathology, Reelin signaling is implicated in protecting against pathological effects of the most common genetic risk factor for late-onset AD, the ⑀4 allele of apolipoprotein E (ApoE4) (reviewed in Refs.31 and 81).”

ApoE has been implicated as a vital factor for synaptic plasticity, neuronal activity, and injury repair.

“ApoE, a critical cholesterol transport protein, has been implicated as a vital factor for synaptic plasticity, neuronal activity, and injury repair124142.”