Relative expression of the p75 neurotrophin receptor, tyrosine receptor kinase A, and insulin receptor in SH-SY5Y neuroblastoma cells and hippocampi from Alzheimer's disease patients

2016 ◽  
Vol 101 ◽  
pp. 22-29 ◽  
Author(s):  
Shingo Ito ◽  
Michel Ménard ◽  
Trevor Atkinson ◽  
Leslie Brown ◽  
James Whitfield ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Insulin Receptor ◽  
Neuroblastoma Cells ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Receptor Kinase ◽  
Relative Expression ◽  
Tyrosine Receptor Kinase ◽  
Kinase A

scholarly journals Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer’s Disease

2021 ◽  
Vol 22 (24) ◽  
pp. 13260
Author(s):  
Klaudia Barabás ◽  
Julianna Kobolák ◽  
Soma Godó ◽  
Tamás Kovács ◽  
Dávid Ernszt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Molecule ◽  
Critical Role ◽  
Live Cell ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Surface Movement ◽  
Human Neurons ◽  
Receptor Dynamics

Neurotrophin receptors such as the tropomyosin receptor kinase A receptor (TrkA) and the low-affinity binding p75 neurotrophin receptor p75NTR play a critical role in neuronal survival and their functions are altered in Alzheimer’s disease (AD). Changes in the dynamics of receptors on the plasma membrane are essential to receptor function. However, whether receptor dynamics are affected in different pathophysiological conditions is unexplored. Using live-cell single-molecule imaging, we examined the surface trafficking of TrkA and p75NTR molecules on live neurons that were derived from human-induced pluripotent stem cells (hiPSCs) of presenilin 1 (PSEN1) mutant familial AD (fAD) patients and non-demented control subjects. Our results show that the surface movement of TrkA and p75NTR and the activation of TrkA- and p75NTR-related phosphoinositide-3-kinase (PI3K)/serine/threonine-protein kinase (AKT) signaling pathways are altered in neurons that are derived from patients suffering from fAD compared to controls. These results provide evidence for altered surface movement of receptors in AD and highlight the importance of investigating receptor dynamics in disease conditions. Uncovering these mechanisms might enable novel therapies for AD.

scholarly journals Reduction of p75 neurotrophin receptor ameliorates the cognitive deficits in a model of Alzheimer's disease

2015 ◽  
Vol 36 (2) ◽  
pp. 740-752 ◽  
Author(s):  
Mark Murphy ◽  
Yvette M. Wilson ◽  
Ernesto Vargas ◽  
Kathryn M. Munro ◽  
Belinda Smith ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Model Of Alzheimer’S Disease

scholarly journals An Intracellular Domain Fragment of the p75 Neurotrophin Receptor (p75NTR) Enhances Tropomyosin Receptor Kinase A (TrkA) Receptor Function

2013 ◽  
Vol 288 (16) ◽  
pp. 11144-11154 ◽  
Author(s):  
Dusan Matusica ◽  
Sune Skeldal ◽  
Alex M. Sykes ◽  
Nickless Palstra ◽  
Aanchal Sharma ◽  
...  
Keyword(s):  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Receptor Kinase ◽  
Receptor Function ◽  
Trka Receptor ◽  
Intracellular Domain ◽  
Kinase A

scholarly journals TrkA-mediated endocytosis of p75-CTF prevents cholinergic neuron death upon γ-secretase inhibition

2021 ◽  
Vol 4 (4) ◽  
pp. e202000844
Author(s):  
María Luisa Franco ◽  
Irmina García-Carpio ◽  
Raquel Comaposada-Baró ◽  
Juan J Escribano-Saiz ◽  
Lucía Chávez-Gutiérrez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Side Effects ◽  
Cholinergic Neurons ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Recognition Sequence ◽  
Neuron Death ◽  
Aged Patients

γ-secretase inhibitors (GSI) were developed to reduce the generation of Aβ peptide to find new Alzheimer’s disease treatments. Clinical trials on Alzheimer’s disease patients, however, showed several side effects that worsened the cognitive symptoms of the treated patients. The observed side effects were partially attributed to Notch signaling. However, the effect on other γ-secretase substrates, such as the p75 neurotrophin receptor (p75NTR) has not been studied in detail. p75NTR is highly expressed in the basal forebrain cholinergic neurons (BFCNs) during all life. Here, we show that GSI treatment induces the oligomerization of p75CTF leading to the cell death of BFCNs, and that this event is dependent on TrkA activity. The oligomerization of p75CTF requires an intact cholesterol recognition sequence (CRAC) and the constitutive binding of TRAF6, which activates the JNK and p38 pathways. Remarkably, TrkA rescues from cell death by a mechanism involving the endocytosis of p75CTF. These results suggest that the inhibition of γ-secretase activity in aged patients, where the expression of TrkA in the BFCNs is already reduced, could accelerate cholinergic dysfunction and promote neurodegeneration.

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