Is amyotrophic lateral sclerosis a primary astrocytic disease?

Sica, R. E. P.

doi:10.1016/j.mehy.2012.08.036

Cited by 10 publications

(10 citation statements)

References 64 publications

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“…Several observations support the idea that there is an early if not primary astrocytic damage in this disease ( Sica, 2012 ).…”

Section: Temporality Cluessupporting

confidence: 55%

“…In the SOD1 G93A transgenic mouse model astroglial atrophy has been described restricted to the astrocytes associated with the affected motor neurons ( Rossi et al, 2008 ). Microglia activation is also increased in ALS and in another SOD1 mouse model Yamanaka et al (2008) demonstrated that it could be modulated by the manipulation of astrocytic behavior ( Yamanaka et al, 2008 ; Lasiene and Yamanaka, 2011 ; Sica, 2012 ).…”

Section: The New Era: Primary Degenerative Disordersmentioning

confidence: 99%

“…Finally, in ALS, astrogliosis both in white and gray matter is a very important hallmark of the illness all along its course ( Yamanaka et al, 2008 ; Lasiene and Yamanaka, 2011 ; Sica, 2012 ). In the SOD1 G93A transgenic mouse model astroglial atrophy has been described restricted to the astrocytes associated with the affected motor neurons ( Rossi et al, 2008 ).…”

Section: The New Era: Primary Degenerative Disordersmentioning

confidence: 99%

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Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System

Capani

Quarracino

Caccuri

et al. 2016

Front. Aging Neurosci.

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Along the last years it has been demonstrated that non-neural cells play a major role in the pathogenesis of the primary degenerative disorders (PDDs) of the human central nervous system. Among them, astrocytes coordinate and participate in many different and complex metabolic processes, in close interaction with neurons. Moreover, increasing experimental evidence hints an early astrocytic dysfunction in these diseases. In this mini review we summarize the astrocytic behavior in PDDs, with special consideration to the experimental observations where astrocytic pathology precedes the development of neuronal dysfunction. We also suggest a different approach that could be consider in human investigations in Alzheimer’s and Parkinson’s disease. We believe that the study of PDDs with human brain samples may hold the key of a paradigmatic physiopathological process in which astrocytes might be the main players.

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“…Several observations support the idea that there is an early if not primary astrocytic damage in this disease ( Sica, 2012 ).…”

Section: Temporality Cluessupporting

confidence: 55%

Section: The New Era: Primary Degenerative Disordersmentioning

confidence: 99%

Section: The New Era: Primary Degenerative Disordersmentioning

confidence: 99%

See 1 more Smart Citation

Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System

Capani

Quarracino

Caccuri

et al. 2016

Front. Aging Neurosci.

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“…In the same study, the authors reported that IL-1 beta and TGF beta-1 cytokines induced collagen IV expression in astrocytes in vitro . Since reactive astrogliosis and microglia activation are major contributors to inflammatory processes in ALS by secretion of various pro-inflammatory cytokines, particularly TNF-alpha and TGF beta-1 (Schiffer et al, 1996; Hall et al, 1998; McGeer and McGeer, 1998; Elliott, 2001; McGeer and McGeer, 2002; Consilvio et al, 2004; Henkel et al, 2004; Xie et al, 2004; Vargas and Johnson, 2010; Appel et al, 2011; Haidet-Phillips et al, 2011; Sica, 2012; Evans et al, 2013; Phatnani et al, 2013) it is possible that reactive astrocytes not only affect motor neurons but also promote a collagenous vascular basement membrane. Moreover, inflammation may initiate barrier damage by impairing endothelial cell function.…”

Section: Similarities and Differences In The B-cns-b Impairment Betwementioning

confidence: 99%

Blood-CNS Barrier Impairment in ALS patients versus an animal model

Garbuzova‐Davis

Sanberg

2014

Front. Cell. Neurosci.

122

100

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Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with a complicated and poorly understood pathogenesis. Recently, alterations in the blood–Central Nervous System barrier (B-CNS-B) have been recognized as a key factor possibly aggravating motor neuron damage. The majority of findings on ALS microvascular pathology have been determined in mutant superoxide dismutase (SOD1) rodent models, identifying barrier damage during disease development which might similarly occur in familial ALS patients carrying the SOD1 mutation. However, our knowledge of B-CNS-B competence in sporadic ALS (SALS) has been limited. We recently showed structural and functional impairment in postmortem gray and white matter microvessels of medulla and spinal cord tissue from SALS patients, suggesting pervasive barrier damage. Although numerous signs of barrier impairment (endothelial cell degeneration, capillary leakage, perivascular edema, downregulation of tight junction proteins, and microhemorrhages) are indicated in both mutant SOD1 animal models of ALS and SALS patients, other pathogenic barrier alterations have as yet only been identified in SALS patients. Pericyte degeneration, perivascular collagen IV expansion, and white matter capillary abnormalities in SALS patients are significant barrier related pathologies yet to be noted in ALS SOD1 animal models. In the current review, these important differences in blood–CNS barrier damage between ALS patients and animal models, which may signify altered barrier transport mechanisms, are discussed. Understanding discrepancies in barrier condition between ALS patients and animal models may be crucial for developing effective therapies.

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“…For example, it has been observed in some amyotrophic lateral sclerosis models that astrocytes either secrete toxic factors [i.e., lipocalin 2 (Bi et al, 2013)] or have a deficiency in providing support to motoneurons, leading to neuronal degeneration. Whether these factors are the main cause of motoneuron loss and how they specifically affect these neurons is still not clear (Sica, 2012; Phatnani et al, 2013). In the case of neurodevelopmental disorders, an altered timing of astrocyte differentiation likely leads to changes in the number of adult astrocytes and/or in their impact upon neurons, as described in more detail below.…”

Section: Introductionmentioning

confidence: 99%

A cellular star atlas: using astrocytes from human pluripotent stem cells for disease studies

Krencik¹,

Ullian²

2013

Front. Cell. Neurosci.

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What roles do astrocytes play in human disease?This question remains unanswered for nearly every human neurological disorder. Yet, because of their abundance and complexity astrocytes can impact neurological function in many ways. The differentiation of human pluripotent stem cells (hPSCs) into neuronal and glial subtypes, including astrocytes, is becoming routine, thus their use as tools for modeling neurodevelopment and disease will provide one important approach to answer this question. When designing experiments, careful consideration must be given to choosing paradigms for differentiation, maturation, and functional analysis of these temporally asynchronous cellular populations in culture. In the case of astrocytes, they display heterogeneous characteristics depending upon species of origin, brain region, developmental stage, environmental factors, and disease states, all of which may render experimental results highly variable. In this review, challenges and future directions are discussed for using hPSC-derived astroglial progenitors and mature astrocytes for neurodevelopmental studies with a focus on exploring human astrocyte effects upon neuronal function. As new technologies emerge to measure the functions of astrocytes in vitro and in vivo, there is also a need for a standardized source of human astrocytes that are most relevant to the diseases of interest.

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Is amyotrophic lateral sclerosis a primary astrocytic disease?

Cited by 10 publications

References 64 publications

Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System

Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System

Blood-CNS Barrier Impairment in ALS patients versus an animal model

A cellular star atlas: using astrocytes from human pluripotent stem cells for disease studies

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