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Neurotrophin receptor p75 mediates the uptake of the amyloid beta (Aβ) peptide, guiding it to lysosomes for degradation in basal forebrain cholinergic neurons

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Neurotrophin receptor p75 mediates the uptake of the amyloid beta (Aβ) peptide, guiding it to lysosomes for degradation in basal forebrain cholinergic neurons

Content Provider	Springer Nature Link
Author	Ovsepian, Saak V. Antyborzec, Inga O’Leary, Valerie B. Zaborszky, Laszlo Herms, Jochen Oliver Dolly, J.
Copyright Year	2013
Abstract	A fascinating yet perhaps overlooked trait of the p75 neurotrophin receptor (p75NTR) is its ability to bind ligands with no obvious neurotrophic function. Using cultured basal forebrain (BF) neurons, this study demonstrates selective internalization of amyloid β (Aβ) 1–42 in conjunction with p75NTR (labelled with IgG192-Cy3) by cholinergic cells. Active under resting conditions, this process was enhanced by high K+ stimulation and was insensitive to inhibitors of regulated synaptic activity—tetrodotoxin or botulinum neurotoxins (BoNT type/A and/B). Blockade of sarco-endoplasmic reticulum (SERCA) Ca2+ ATPase with thapsigargin and CPA or chelation of Ca2+ with EGTA-AM strongly suppressed the endocytosis of p75NTR, implicating the role of ER released Ca2+. The uptake of IgG192-Cy3 was also reduced by T-type Ca2+ channel blocker mibefradil but not Cd2+, an indiscriminate blocker of high voltage-activated Ca2+ currents. A strong co-localization of IgG192-Cy3 with late endosome (Rab7) or lysosome (Lamp1) qualifier proteins suggest these compartments as the primary destination for internalized IgG192 and Aβ. Selective uptake and labeling of BF cholinergic cells with IgG192-Cy3 injected into the prefrontal cortex was verified also in vivo. The significance of these findings in relation to Aβ clearance in the cerebral cortex and pathophysiology of Alzheimer’s disease is discussed.
Starting Page	1527
Ending Page	1541
Page Count	15
File Format	PDF
ISSN	18632653
Journal	Anatomy and Embryology
Volume Number	219
Issue Number	5
e-ISSN	18632661
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2013-05-29
Publisher Place	Berlin/Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	p75 NTR Basal forebrain cholinergic neurons Lysosomal degradation Calcium Amyloid β clearance Alzheimer’s disease Neurosciences Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Anatomy Histology

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