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Microglia receptors and their implications in the response to amyloid β for Alzheimer's disease pathogenesis.

Doens D, Fernández PL - J Neuroinflammation (2014)

Bottom Line: For many years, research has been focused on Aβ accumulation in senile plaques, as these aggregations were perceived as the main cause of the neurodegeneration found in AD.Aβ activates microglia through a variety of innate immune receptors expressed on these cells.The mechanisms through which amyloid deposits provoke an inflammatory response are not fully understood, but it is believed that these receptors cooperate in the recognition, internalization, and clearance of Aβ and in cell activation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centro de Biología Molecular y Celular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Edificio 219, Clayton, Ciudad del Saber, República de Panamá. pllanes@indicasat.org.pa.

ABSTRACT
Alzheimer's disease (AD) is a major public health problem with substantial economic and social impacts around the world. The hallmarks of AD pathogenesis include deposition of amyloid β (Aβ), neurofibrillary tangles, and neuroinflammation. For many years, research has been focused on Aβ accumulation in senile plaques, as these aggregations were perceived as the main cause of the neurodegeneration found in AD. However, increasing evidence suggests that inflammation also plays a critical role in the pathogenesis of AD. Microglia cells are the resident macrophages of the brain and act as the first line of defense in the central nervous system. In AD, microglia play a dual role in disease progression, being essential for clearing Aβ deposits and releasing cytotoxic mediators. Aβ activates microglia through a variety of innate immune receptors expressed on these cells. The mechanisms through which amyloid deposits provoke an inflammatory response are not fully understood, but it is believed that these receptors cooperate in the recognition, internalization, and clearance of Aβ and in cell activation. In this review, we discuss the role of several receptors expressed on microglia in Aβ recognition, uptake, and signaling, and their implications for AD pathogenesis.

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Related in: MedlinePlus

Microglia receptors involved in the amyloid cascade. A variety of microglia receptors are involved in Aβ clearance and in triggering an inflammatory response. Some receptors (RAGE, NLRP3) are mainly implicated in the generation of an inflammatory response by triggering a signaling cascade that results in the production of proinflammatory mediators. Other receptors (SR-AI, TREM2) are involved in the clearance of Aβ by inducing internalization of Aβ fibrils. Some receptors (complement receptors, Fc receptors, FPRL1/FPR2, CD36, TLRs) are involved in both processes. CD33 seems to promote Aβ accumulation.
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Figure 1: Microglia receptors involved in the amyloid cascade. A variety of microglia receptors are involved in Aβ clearance and in triggering an inflammatory response. Some receptors (RAGE, NLRP3) are mainly implicated in the generation of an inflammatory response by triggering a signaling cascade that results in the production of proinflammatory mediators. Other receptors (SR-AI, TREM2) are involved in the clearance of Aβ by inducing internalization of Aβ fibrils. Some receptors (complement receptors, Fc receptors, FPRL1/FPR2, CD36, TLRs) are involved in both processes. CD33 seems to promote Aβ accumulation.

Mentions: The mechanisms through which amyloid deposits provoke inflammation are not fully understood. Microglia cells express several receptors that cooperate in the recognition, internalization, and clearance of Aβ and in cell activation. Microglia receptors, such as scavenger receptors (SR-AI/II), CD36, RAGE (receptor for advanced glycosylation endproducts), Fc receptors, TLRs (toll-like receptors), and complement receptors are involved in these processes [12-14] (Figure 1). This review will examine the various roles of microglia receptors in the amyloid cascade, and the implications for AD.


Microglia receptors and their implications in the response to amyloid β for Alzheimer's disease pathogenesis.

Doens D, Fernández PL - J Neuroinflammation (2014)

Microglia receptors involved in the amyloid cascade. A variety of microglia receptors are involved in Aβ clearance and in triggering an inflammatory response. Some receptors (RAGE, NLRP3) are mainly implicated in the generation of an inflammatory response by triggering a signaling cascade that results in the production of proinflammatory mediators. Other receptors (SR-AI, TREM2) are involved in the clearance of Aβ by inducing internalization of Aβ fibrils. Some receptors (complement receptors, Fc receptors, FPRL1/FPR2, CD36, TLRs) are involved in both processes. CD33 seems to promote Aβ accumulation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3975152&req=5

Figure 1: Microglia receptors involved in the amyloid cascade. A variety of microglia receptors are involved in Aβ clearance and in triggering an inflammatory response. Some receptors (RAGE, NLRP3) are mainly implicated in the generation of an inflammatory response by triggering a signaling cascade that results in the production of proinflammatory mediators. Other receptors (SR-AI, TREM2) are involved in the clearance of Aβ by inducing internalization of Aβ fibrils. Some receptors (complement receptors, Fc receptors, FPRL1/FPR2, CD36, TLRs) are involved in both processes. CD33 seems to promote Aβ accumulation.
Mentions: The mechanisms through which amyloid deposits provoke inflammation are not fully understood. Microglia cells express several receptors that cooperate in the recognition, internalization, and clearance of Aβ and in cell activation. Microglia receptors, such as scavenger receptors (SR-AI/II), CD36, RAGE (receptor for advanced glycosylation endproducts), Fc receptors, TLRs (toll-like receptors), and complement receptors are involved in these processes [12-14] (Figure 1). This review will examine the various roles of microglia receptors in the amyloid cascade, and the implications for AD.

Bottom Line: For many years, research has been focused on Aβ accumulation in senile plaques, as these aggregations were perceived as the main cause of the neurodegeneration found in AD.Aβ activates microglia through a variety of innate immune receptors expressed on these cells.The mechanisms through which amyloid deposits provoke an inflammatory response are not fully understood, but it is believed that these receptors cooperate in the recognition, internalization, and clearance of Aβ and in cell activation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centro de Biología Molecular y Celular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Edificio 219, Clayton, Ciudad del Saber, República de Panamá. pllanes@indicasat.org.pa.

ABSTRACT
Alzheimer's disease (AD) is a major public health problem with substantial economic and social impacts around the world. The hallmarks of AD pathogenesis include deposition of amyloid β (Aβ), neurofibrillary tangles, and neuroinflammation. For many years, research has been focused on Aβ accumulation in senile plaques, as these aggregations were perceived as the main cause of the neurodegeneration found in AD. However, increasing evidence suggests that inflammation also plays a critical role in the pathogenesis of AD. Microglia cells are the resident macrophages of the brain and act as the first line of defense in the central nervous system. In AD, microglia play a dual role in disease progression, being essential for clearing Aβ deposits and releasing cytotoxic mediators. Aβ activates microglia through a variety of innate immune receptors expressed on these cells. The mechanisms through which amyloid deposits provoke an inflammatory response are not fully understood, but it is believed that these receptors cooperate in the recognition, internalization, and clearance of Aβ and in cell activation. In this review, we discuss the role of several receptors expressed on microglia in Aβ recognition, uptake, and signaling, and their implications for AD pathogenesis.

Show MeSH
Related in: MedlinePlus