An update on human astrocytes and their role in development and disease

Majo, Martina de; Koontz, Mark; Rowitch, David H.; Ullian, Erik M.

doi:10.1002/glia.23771

Cited by 48 publications

(48 citation statements)

References 221 publications

(310 reference statements)

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“…These studies highlight the role that malfunctioning astrocytes play in the spread of α-syn, accumulating abnormal levels due to impaired protein degradation which may enhance the spread of PD in the brain. As the SNpc region has the lowest astrocyte to neuron ratio in the CNS (Damier et al, 1993), this may explain why dopaminergic neurons are susceptible to PD as they have less astrocytic support than neurons in other regions (de Majo et al, 2020).…”

Section: Parkinson's Diseasementioning

confidence: 99%

Neuromodulation of Glial Function During Neurodegeneration

Stevenson

Samokhina

Rossetti

et al. 2020

Front. Cell. Neurosci.

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Glia, a non-excitable cell type once considered merely as the connective tissue between neurons, is nowadays acknowledged for its essential contribution to multiple physiological processes including learning, memory formation, excitability, synaptic plasticity, ion homeostasis, and energy metabolism. Moreover, as glia are key players in the brain immune system and provide structural and nutritional support for neurons, they are intimately involved in multiple neurological disorders. Recent advances have demonstrated that glial cells, specifically microglia and astroglia, are involved in several neurodegenerative diseases including Amyotrophic lateral sclerosis (ALS), Epilepsy, Parkinson's disease (PD), Alzheimer's disease (AD), and frontotemporal dementia (FTD). While there is compelling evidence for glial modulation of synaptic formation and regulation that affect neuronal signal processing and activity, in this manuscript we will review recent findings on neuronal activity that affect glial function, specifically during neurodegenerative disorders. We will discuss the nature of each glial malfunction, its specificity to each disorder, overall contribution to the disease progression and assess its potential as a future therapeutic target.

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Section: Parkinson's Diseasementioning

confidence: 99%

Neuromodulation of Glial Function During Neurodegeneration

Stevenson

Samokhina

Rossetti

et al. 2020

Front. Cell. Neurosci.

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“…In animal models of these disorders, there has been much focus on neuronal deficits and underlying mechanisms. However, given the roles astrocytes play in the brain, it is not surprising that a growing number of studies have highlighted the contribution of astrocytes to disease pathophysiology at the molecular, cellular, and functional levels [113][114][115][116]. Here, we will describe studies that use astrocytes derived from iPSCs of patients with neurodevelopmental disorders and compare them with findings from animal models, attempting to identify the validated and novel phenotypes as well as highlight the knowledge gaps and future directions in this rapidly developing field.…”

Section: Modeling Astrocytes In Neurodevelopmental Disordersmentioning

confidence: 99%

Modeling Neurodevelopmental and Neuropsychiatric Diseases with Astrocytes Derived from Human-Induced Pluripotent Stem Cells

Ren

Dunaevsky

2021

IJMS

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Accumulating studies demonstrate the morphological and functional diversity of astrocytes, a subtype of glial cells in the central nervous system. Animal models are instrumental in advancing our understanding of the role of astrocytes in brain development and their contribution to neurological disease; however, substantial interspecies differences exist between rodent and human astrocytes, underscoring the importance of studying human astrocytes. Human pluripotent stem cell differentiation approaches allow the study of patient-specific astrocytes in the etiology of neurological disorders. In this review, we summarize the structural and functional properties of astrocytes, including the unique features of human astrocytes; demonstrate the necessity of the stem cell platform; and discuss how this platform has been applied to the research of neurodevelopmental and neuropsychiatric diseases.

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“…[121][122][123] Although most effort has been placed on the effects of iron on neurons, it is now well-accepted that dysfunction of glial cells makes key contributions to the pathogenesis of neurodegenerative disorders. [124][125][126][127] Iron is required for the proper development of oligodendrocytes and a high amount of ferritin-bound iron is necessary for synthesis of myelin and fatty acid synthesis. 128 Abnormalities in oligodendrocytes, including effects on the production and maintenance of myelination, are a feature of various neurodegenerative diseases.…”

Section: Age-associated Neurodegenerative Diseasesmentioning

confidence: 99%

Overdosing on iron: Elevated iron and degenerative brain disorders

D’Mello¹,

Kindy

2020

Exp Biol Med (Maywood)

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All cells in organisms ranging from yeast to humans utilize iron as a cofactor or structural element of proteins that function in diverse and critical cellular functions. However, deregulation of the homeostatic mechanisms regulating iron metabolism resulting in a reduction or excess of iron within the cell or outside of it can have serious effects to the health of cells and the organism. This review provides a brief overview of the molecular and cellular mechanisms regulating iron physiology, including the molecules and processes regulating iron uptake, its storage and utilization, its recycling, and its release from the cell, such that the cellular iron levels are sufficient to meet metabolic demand but below those that cause permanent damage. The major focus of review is on the pathological consequences of dysregulation of these homeostatic mechanisms, focusing on the brain. Current advances on the role of iron accumulation to the pathogenesis of rare neurological disorders caused by genetic mutations as well as to the more prevalent and age-associated neurodegenerative diseases are described. Impact statement Brain degenerative disorders, which include some neurodevelopmental disorders and age-associated diseases, cause debilitating neurological deficits and are generally fatal. A large body of emerging evidence indicates that iron accumulation in neurons within specific regions of the brain plays an important role in the pathogenesis of many of these disorders. Iron homeostasis is a highly complex and incompletely understood process involving a large number of regulatory molecules. Our review provides a description of what is known about how iron is obtained by the body and brain and how defects in the homeostatic processes could contribute to the development of brain diseases, focusing on Alzheimer’s disease and Parkinson’s disease as well as four other disorders belonging to a class of inherited conditions referred to as neurodegeneration based on iron accumulation (NBIA) disorders. A description of potential therapeutic approaches being tested for each of these different disorders is provided.

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An update on human astrocytes and their role in development and disease

Cited by 48 publications

References 221 publications

Neuromodulation of Glial Function During Neurodegeneration

Neuromodulation of Glial Function During Neurodegeneration

Modeling Neurodevelopmental and Neuropsychiatric Diseases with Astrocytes Derived from Human-Induced Pluripotent Stem Cells

Overdosing on iron: Elevated iron and degenerative brain disorders

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