Heterogeneity of Neuroinflammatory Responses in Amyotrophic Lateral Sclerosis: A Challenge or an Opportunity?

Cipollina, Giada; Serej, Arash Davari; Nolfi, Gianluca Di; Gazzano, Andrea; Marsala, Andrea; Spatafora, Mauro G; Peviani, Marco

doi:10.3390/ijms21217923

Cited by 17 publications

(13 citation statements)

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“…Understanding the mechanism to regulate the switch from a neurotoxic phenotype to a neurosupportive one is essential for developing efficacious therapies. In other words, elucidation of the transforming mechanism of neuroinflammatory response could guide future treatments in ALS (Cipollina et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Stromal Cell Antigen 2: Is a Potential Neuroinflammation Biomarker of SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis in Pre-symptomatic Stage

Zhang

et al. 2022

Front. Neurosci.

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Neuroinflammation has long been thought to be associated with amyotrophic lateral sclerosis (ALS) development and progression. However, the exact molecular mechanisms of neuroinflammation underlying ALS remain largely unknown. In the present study, we attempted to elucidate the genetic basis of neuroinflammation in ALS by comparing the transcriptomic profile of the anterior horns of the lumbar spinal cord (AHLSC) between SOD1G93A mice and their wild-type (WT) littermates. Our results revealed that immune-related genes were selectively up-regulated in the AHLSC of pre-symptomatic ALS mice (40 days of age) compared to age-matched WT control mice. Notably, the differential expression level of these immune-related genes became more significant at the symptomatic stage of disease (90 days of age) in the ALS mice. Subsequently, eight genes involved in innate immune response in the AHLSC of ALS mice were further validated by qRT-PCR analysis. Of these genes, bone marrow stromal cell antigen 2 (BST2) was found for the first time to be significantly higher in the AHLSC of pre-symptomatic ALS mice when compared with WT mice. The increasing trend of BST2 expression became more obvious in the symptomatic stage. Immunofluorescent staining further confirmed that BST2 is mainly expressed on microglia in the AHLSC of ALS mice. These findings support the view that immune-related neuroinflammation is involved in the early pathogenesis of ALS, and BST2 may serve as a potential target for ameliorating microglia-mediated neuroinflammation pathologies in ALS.

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Section: Discussionmentioning

confidence: 99%

Bone Marrow Stromal Cell Antigen 2: Is a Potential Neuroinflammation Biomarker of SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis in Pre-symptomatic Stage

Zhang

et al. 2022

Front. Neurosci.

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“…Neuroinflammation plays an essential role in all ALS patients. Due to the heterogeneity of the disease, it is mandatory to investigate the diverse roles of microglia, as reviewed by Cipollina et al, 2020, in many different models of ALS [110]. After all, this is the basis for finding an appropriate therapy for different ALS cohorts.…”

Section: Discussionmentioning

confidence: 99%

Little Helpers or Mean Rogue—Role of Microglia in Animal Models of Amyotrophic Lateral Sclerosis

Cihankaya

Theiß

Matschke

2021

IJMS

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Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, causing degeneration of both upper and lower motor neurons in the central nervous system (CNS). ALS patients suffer from hyperreflexia, spasticity, paralysis and muscle atrophy and typically die due to respiratory failure 1–5 years after disease onset. In addition to the degeneration of motor neurons on the cellular level, ALS has been associated with neuroinflammation, such as microgliosis. Microglial activation in ALS can either be protective or degenerative to the neurons. Among others, mutations in superoxide dismutase 1 (SOD1), chromosome 9 open reading frame 72 (C9Orf72), transactive response DNA binding protein (TDP) 43 and vacuolar protein sorting-associated protein 54 (VPS54) genes have been associated with ALS. Here, we describe the dual role and functionality of microglia in four different in vivo ALS models and search for the lowest common denominator with respect to the role of microglia in the highly heterogeneous disease of ALS.

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“…ALS occurrence has been linked to different factors including genetic factors, mitochondrial diseases and oxidative stress ( Blasco et al, 2014 ). This disease is still incurable despite the high number of clinical trials for potential therapies, that were all proven to be negative ( Cipollina et al, 2020 ).…”

Section: Using Mscs In the Treatment Of Other Neurodegenerative Diseasesmentioning

confidence: 99%

Mesenchymal Stem Cell-Based Therapy for Lysosomal Storage Diseases and Other Neurodegenerative Disorders

et al. 2022

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Lysosomal storage diseases (LSDs) are a group of approximately 50 genetic disorders caused by mutations in genes coding enzymes that are involved in cell degradation and transferring lipids and other macromolecules. Accumulation of lipids and other macromolecules in lysosomes leads to the destruction of affected cells. Although the clinical manifestations of different LSDs vary greatly, more than half of LSDs have symptoms of central nervous system neurodegeneration, and within each disorder there is a considerable variation, ranging from severe, infantile-onset forms to attenuated adult-onset disease, sometimes with distinct clinical features. To date, treatment options for this group of diseases remain limited, which highlights the need for further development of innovative therapeutic approaches, that can not only improve the patients’ quality of life, but also provide full recovery for them. In many LSDs stem cell-based therapy showed promising results in preclinical researches. This review discusses using mesenchymal stem cells for different LSDs therapy and other neurodegenerative diseases and their possible limitations.

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Heterogeneity of Neuroinflammatory Responses in Amyotrophic Lateral Sclerosis: A Challenge or an Opportunity?

Cited by 17 publications

References 135 publications

Bone Marrow Stromal Cell Antigen 2: Is a Potential Neuroinflammation Biomarker of SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis in Pre-symptomatic Stage

Bone Marrow Stromal Cell Antigen 2: Is a Potential Neuroinflammation Biomarker of SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis in Pre-symptomatic Stage

Little Helpers or Mean Rogue—Role of Microglia in Animal Models of Amyotrophic Lateral Sclerosis

Mesenchymal Stem Cell-Based Therapy for Lysosomal Storage Diseases and Other Neurodegenerative Disorders

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