P75 Neurotrophin Receptor in the Nucleus Basalis of Meynert in Relation to Age, Sex, and Alzheimer's Disease

2000 ◽  
Vol 161 (1) ◽  
pp. 245-258 ◽  
Author(s):  
Ahmad Salehi ◽  
Marta Ocampo ◽  
Joost Verhaagen ◽  
Dick F. Swaab
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor

scholarly journals Role of Tyrosine Phosphorylation in The Antioxidant Effects of The P75 Neurotrophin Receptor

2009 ◽  
Vol 2 (4) ◽  
pp. 238-246 ◽  
Author(s):  
Tong Zhang ◽  
Zhiping Mi ◽  
Nina F. Schor
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidant Stress ◽  
Cholinergic Neurons ◽  
Adult Brain ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert ◽  
Differential Sensitivity ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor

The p75 neurotrophin receptor (p75NTR) is an α-and γ-secretase substrate expressed preferentially in the cholinergic neurons of the nucleus basalis of Meynert, the hippocampus, and the cerebellum of the adult brain. Mutations of the γ-secretase, presenilin, have been implicated in familial Alzheimer's disease. Furthermore, oxidative and inflammatory injury to the cholinergic neurons of the nucleus basalis of Meynert and hippocampus plays a critical role in the pathology of Alzheimer's disease. The intracellular domain of p75NTR (p75ICD) is the α- and γ-secretase cleavage fragment of the holoreceptor that functions as an antioxidant in PC12 rat pheochromocytoma cells. Phosphorylation of the receptor is thought to be necessary for many of its functions, and two tyrosines in p75ICD have been among the functionally important phosphorylation sites. Site-directed mutagenesis was used to generate three p75ICD mutants that cannot be phosphorylated at either or both tyrosines, respectively. Each of these mutants was expressed in p75NTR-deficient PC12 cells to determine the effects of blocking phosphorylation at specific sites on the antioxidant activity of p75ICD. Interfering with phosphorylation at tyrosine-337 impairs antioxidant function, while interfering with phosphorylation at tyrosine-366 does not, and may in fact impart protection from oxidant stress. Neither MAPK (i.e., p38, ERK1, ERK2) content nor NF-κB activation accounts for the differential sensitivity to oxidant stress among the differentially phosphorylated p75NTR cell lines. However, differences in the time course of ERK1,2 phosphorylation among the lines account in large measure for their differential oxidant sensitivity. The phosphorylation state of specific sites on p75ICD may modulate the resistance of neurons in Alzheimer's disease-relevant brain regions to oxidant stress.

scholarly journals Functional connectivity of the nucleus basalis of Meynert in Lewy body dementia and Alzheimer’s disease

2021 ◽  
pp. 1-6
Author(s):  
Julia Schumacher ◽  
Alan J. Thomas ◽  
Luis R. Peraza ◽  
Michael Firbank ◽  
John T. O’Brien ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Lewy Body ◽  
Cholinergic System ◽  
Structural Changes ◽  
Lewy Body Dementia ◽  
Occipital Cortex ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert

ABSTRACT Cholinergic deficits are a hallmark of Alzheimer’s disease (AD) and Lewy body dementia (LBD). The nucleus basalis of Meynert (NBM) provides the major source of cortical cholinergic input; studying its functional connectivity might, therefore, provide a tool for probing the cholinergic system and its degeneration in neurodegenerative diseases. Forty-six LBD patients, 29 AD patients, and 31 healthy age-matched controls underwent resting-state functional magnetic resonance imaging (fMRI). A seed-based analysis was applied with seeds in the left and right NBM to assess functional connectivity between the NBM and the rest of the brain. We found a shift from anticorrelation in controls to positive correlations in LBD between the right/left NBM and clusters in right/left occipital cortex. Our results indicate that there is an imbalance in functional connectivity between the NBM and primary visual areas in LBD, which provides new insights into alterations within a part of the corticopetal cholinergic system that go beyond structural changes.

scholarly journals Potential for intermittent stimulation of nucleus basalis of Meynert to impact treatment of alzheimer's disease

2017 ◽  
Vol 10 (5-6) ◽  
pp. e1389359 ◽  
Author(s):  
David T. Blake ◽  
Alvin V. Terry ◽  
Marc Plagenhoef ◽  
Christos Constantinidis ◽  
Ruifeng Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert ◽  
Intermittent Stimulation ◽  
Stimulation Of

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.

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