Glial phagocytic clearance in Parkinson’s disease

Tremblay, Marie‐Ève; Cookson, Mark; Civiero, Laura

doi:10.1186/s13024-019-0314-8

Cited by 117 publications

(104 citation statements)

References 165 publications

(177 reference statements)

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“…The mechanism(s) by which immune cells phagocytose debris involves the binding of scavenger receptors to the surface of dead or dying cells. There are a range of scavenger receptors expressed by mononuclear phagocytes, and abnormalities in some of these scavenger receptors have been implicated in other age‐related diseases of the CNS including Alzheimer's disease and Parkinson's disease . One receptor that has received some attention for its role in removal of debris is the P2X 7 receptor.…”

Section: The Role Of Scavenger Receptors In the Development Of Early Amdmentioning

confidence: 99%

Contribution of microglia and monocytes to the development and progression of age related macular degeneration

Fletcher

2020

Ophthalmic Physiologic Optic

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Purpose Age related macular degeneration (AMD) is the leading cause of irreversible vision loss in industrialised nations. Based on genetics, as well as proteome analysis of drusen, the role the innate immune system in the development and/or progression of the disease is well established. Mononuclear phagocytes, such as microglia and monocytes, play critical roles in innate immunity. Here, the role of retinal microglia in mediating normal retinal function, and how these cells change with age is discussed, so as to understand their role in the development and progression of AMD. Recent findings It is now known that microglia dynamically survey the neural environment, responding rapidly to even the most subtle neural injury. The dynamic and phagocytic roles of microglia can change with age contributing to alteration in the response of these cells to damage with age. Accumulation of innate immune cells in the subretinal space is a hallmark feature of the development of AMD, reflecting either an increase in migration of monocytes into the retina, or a failure of immune cell elimination from the retina. Furthermore, changes in phagocytic ability of immune cells could contribute to the accumulation of drusen deposits in the posterior eye. Summary An overview of how retinal microglia maintain retinal homeostasis under normal conditions is provided, and then how they contribute to each stage of AMD. In addition, circulating monocytes are altered in those with AMD, contributing to the overall inflammatory state. Understanding the role of cells of the innate immune system in AMD may uncover novel therapeutic targets with which to reduce either the development or progression of disease.

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Section: The Role Of Scavenger Receptors In the Development Of Early Amdmentioning

confidence: 99%

Contribution of microglia and monocytes to the development and progression of age related macular degeneration

Fletcher

2020

Ophthalmic Physiologic Optic

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“…The phagocytosis of apoptotic cell debris can induce various effects. In some cases, neuronal material is accumulated within lysosomes, with ensuing defects of the organelle with the extracellular release of toxic debris [ 92 ]. In other conditions, the uptake of Aβ within astrocytes results in digestion and, thus, in the control of its level [ 93 ].…”

Section: The Role Of Astrocytes In Alzheimer’s Diseasementioning

confidence: 99%

Astrocytes: News about Brain Health and Diseases

Meldolesi

2020

Biomedicines

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Astrocytes, the most numerous glial cells in the brains of humans and other mammalian animals, have been studied since their discovery over 100 years ago. For many decades, however, astrocytes were believed to operate as a glue, providing only mechanical and metabolic support to adjacent neurons. Starting from a “revolution” initiated about 25 years ago, numerous astrocyte functions have been reconsidered, some previously unknown, others attributed to neurons or other cell types. The knowledge of astrocytes has been continuously growing during the last few years. Based on these considerations, in the present review, different from single or general overviews, focused on six astrocyte functions, chosen due in their relevance in both brain physiology and pathology. Astrocytes, previously believed to be homogeneous, are now recognized to be heterogeneous, composed by types distinct in structure, distribution, and function; their cooperation with microglia is known to govern local neuroinflammation and brain restoration upon traumatic injuries; and astrocyte senescence is relevant for the development of both health and diseases. Knowledge regarding the role of astrocytes in tauopathies and Alzheimer’s disease has grow considerably. The multiple properties emphasized here, relevant for the present state of astrocytes, will be further developed by ongoing and future studies.

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“…Growing evidence suggests a possible involvement of astrocytes and microglia cells in the pathogenesis of PD alongside DA neurons because of their active role in phagocytic cleaning processes and modulation of inflammation as well as for the expression of PD genes in glia cells (Tremblay et al ; Booth et al ).…”

Section: Role Of Lrrk2 In the Endolysosomal Compartments In Glial Cellsmentioning

confidence: 99%

“…In contrast to microglia, astrocytes are considered non‐professional phagocytes (Galloway et al ). However, recent advances highlighted a possible involvement of these cells in the clean‐up of extracellular space from debris, damaged synapses, apoptotic cells, protein aggregates and possible pathogens (Galloway et al ; Tremblay et al ; Morales et al ). Also in the case of astrocytes, several studies have highlighted the ability of these cells to internalize and digest α‐syn (Lindström et al ; Loria et al ; Sacino et al ).…”

Section: Role Of Lrrk2 In the Endolysosomal Compartments In Glial Cellsmentioning

confidence: 99%

Leucine‐rich repeat kinase 2 and lysosomal dyshomeostasis in Parkinson disease

Cogo

Manzoni

Lewis

et al. 2019

Journal of Neurochemistry

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Over the last two decades, a number of studies have underlined the importance of lysosomal-based degradative pathways in maintaining the homeostasis of post-mitotic cells, and revealed the remarkable contribution of a functional autophagic machinery in the promotion of longevity. In contrast, defects in the clearance of organelles and aberrant protein aggregates have been linked to accelerated neuronal loss and neurological dysfunction. Several neurodegenerative disorders, among which Alzheimer disease (AD), Frontotemporal dementia, and Amyotrophic Lateral Sclerosis to name a few, are associated with alterations of the autophagy and endo-lysosomal pathways. In Parkinson disease (PD), the most prevalent genetic determinant, Leucine-rich repeat kinase 2 (LRRK2), is believed to be involved in the regulation of intracellular vesicle traffic, autophagy and lysosomal function. Here, we review the current understanding of the mechanisms by which LRRK2 regulates lysosomal-based degradative pathways in neuronal and non-neuronal cells and discuss the impact of pathogenic PD mutations in contributing to lysosomal dyshomeostasis.

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Glial phagocytic clearance in Parkinson’s disease

Cited by 117 publications

References 165 publications

Contribution of microglia and monocytes to the development and progression of age related macular degeneration

Contribution of microglia and monocytes to the development and progression of age related macular degeneration

Astrocytes: News about Brain Health and Diseases

Leucine‐rich repeat kinase 2 and lysosomal dyshomeostasis in Parkinson disease

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