scholarly journals Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Zoran Boskovic ◽  
Sonja Meier ◽  
Yunpeng Wang ◽  
Michael R. Milne ◽  
Tessa Onraet ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Neuronal Development ◽  
Critical Role ◽  
Neurotrophin Receptor ◽  
Current Evidence ◽  
P75 Neurotrophin Receptor ◽  
Neurotrophin Receptors ◽  
Cortical Function ◽  
Cholinergic Basal Forebrain ◽  
And Function

Abstract Cholinergic basal forebrain (cBF) neurons are defined by their expression of the p75 neurotrophin receptor (p75NTR) and tropomyosin-related kinase (Trk) neurotrophin receptors in addition to cholinergic markers. It is known that the neurotrophins, particularly nerve growth factor (NGF), mediate cholinergic neuronal development and maintenance. However, the role of neurotrophin signalling in regulating adult cBF function is less clear, although in dementia, trophic signalling is reduced and p75NTR mediates neurodegeneration of cBF neurons. Here we review the current understanding of how cBF neurons are regulated by neurotrophins which activate p75NTR and TrkA, B or C to influence the critical role that these neurons play in normal cortical function, particularly higher order cognition. Specifically, we describe the current evidence that neurotrophins regulate the development of basal forebrain neurons and their role in maintaining and modifying mature basal forebrain synaptic and cortical microcircuit connectivity. Understanding the role neurotrophin signalling plays in regulating the precision of cholinergic connectivity will contribute to the understanding of normal cognitive processes and will likely provide additional ideas for designing improved therapies for the treatment of neurological disease in which cholinergic dysfunction has been demonstrated.

scholarly journals PPARγExpression and Function in Mycobacterial Infection: Roles in Lipid Metabolism, Immunity, and Bacterial Killing

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Patricia E. Almeida ◽  
Alan Brito Carneiro ◽  
Adriana R. Silva ◽  
Patricia T. Bozza
Keyword(s):  
Molecular Mechanisms ◽  
Critical Role ◽  
Mycobacterial Infection ◽  
Receptor Activation ◽  
Host Cells ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Bacterial Killing ◽  
Peroxisome Proliferator Activated Receptor ◽  
And Function

Tuberculosis continues to be a global health threat, with drug resistance and HIV coinfection presenting challenges for its control.Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a highly adapted pathogen that has evolved different strategies to subvert the immune and metabolic responses of host cells. Although the significance of peroxisome proliferator-activated receptor gamma (PPARγ) activation by mycobacteria is not fully understood, recent findings are beginning to uncover a critical role for PPARγduring mycobacterial infection. Here, we will review the molecular mechanisms that regulate PPARγexpression and function during mycobacterial infection. Current evidence indicates that mycobacterial infection causes a time-dependent increase in PPARγexpression through mechanisms that involve pattern recognition receptor activation. Mycobacterial triggered increased PPARγexpression and activation lead to increased lipid droplet formation and downmodulation of macrophage response, suggesting that PPARγexpression might aid the mycobacteria in circumventing the host response acting as an escape mechanism. Indeed, inhibition of PPARγenhances mycobacterial killing capacity of macrophages, suggesting a role of PPARγin favoring the establishment of chronic infection. Collectively, PPARγis emerging as a regulator of tuberculosis pathogenesis and an attractive target for the development of adjunctive tuberculosis therapies.

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 The p75 neurotrophin receptor is required for the survival of neuronal progenitors and normal formation of the basal forebrain, striatum, thalamus and neocortex

Development ◽  
2019 ◽  
Vol 146 (18) ◽  
pp. dev181933 ◽  
Author(s):  
Sonja Meier ◽  
Fabienne Alfonsi ◽  
Nyoman D. Kurniawan ◽  
Michael R. Milne ◽  
Maria A. Kasherman ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Neuronal Progenitors

scholarly journals Neurotrophin Regulation of Gene Expression

1997 ◽  
Vol 24 (04) ◽  
pp. 272-283 ◽  
Author(s):  
Azad Bonni ◽  
Michael E. Greenberg
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Neuronal Survival ◽  
Regulation Of Gene Expression ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Neurotrophin Receptors ◽  
Important Target ◽  
The Subject ◽  
Induced Changes

ABSTRACT:The neurotrophins comprise a family of secreted proteins that elicit profound responses in cells of the developing and mature vertebrate nervous system including the regulation of neuronal survival and differentiation. The molecular mechanisms by which the neurotrophins exert their effects have been the subject of intense investigation. The neurotrophins elicit responses in neurons via members of the Trk family of receptors and the p75 neurotrophin receptor. Once activated, neurotrophin receptors trigger a large number of biochemical events that propagate the neurotrophin signal from the plasma membrane to the interior of the cell. An important target of the neurotrophin-induced signaling pathways is the nucleus, where neurotrophin-induced signals are coupled to alterations in gene expression. These neurotrophin-induced changes in gene expression are critical for many of. the phenotypic effects of neurotrophins including the regulation of neuronal survival and differentiation.

scholarly journals cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development

2018 ◽  
Vol 115 (40) ◽  
pp. E9449-E9458 ◽  
Author(s):  
Feng Zhang ◽  
Yaqing Wang ◽  
Tao Wang ◽  
Li Yao ◽  
Sin Man Lam ◽  
...  
Keyword(s):  
Brain Development ◽  
Neural Development ◽  
Neuronal Development ◽  
Critical Role ◽  
Conditional Knockout ◽  
Copii Vesicle ◽  
Membrane Components ◽  
And Function ◽  
Cellular Components ◽  
Abnormal Behaviors

Normal neural development is essential for the formation of neuronal networks and brain function. Cutaneous T cell lymphoma-associated antigen 5 (cTAGE5)/meningioma expressed antigen 6 (MEA6) plays a critical role in the secretion of proteins. However, its roles in the transport of nonsecretory cellular components and in brain development remain unknown. Here, we show that cTAGE5/MEA6 is important for brain development and function. Conditional knockout ofcTAGE5/MEA6in the brain leads to severe defects in neural development, including deficits in dendrite outgrowth and branching, spine formation and maintenance, astrocyte activation, and abnormal behaviors. We reveal that loss of cTAGE5/MEA6 affects the interaction between the coat protein complex II (COPII) components, SAR1 and SEC23, leading to persistent activation of SAR1 and defects in COPII vesicle formation and transport from the endoplasmic reticulum to the Golgi, as well as disturbed trafficking of membrane components in neurons. These defects affect not only the transport of materials required for the development of dendrites and spines but also the signaling pathways required for neuronal development. Because mutations in cTAGE5/MEA6 have been found in patients with Fahr’s disease, our study potentially also provides insight into the pathogenesis of this disorder.

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