Endogenous retroviruses in ALS: A reawakening?

Brown, Robert H.; Al‐Chalabi, Ammar

doi:10.1126/scitranslmed.aad3533

Cited by 11 publications

(7 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Alternatively, there is increasing interest in exogenous factors that might trigger sporadic neurodegeneration. It has been proposed that atypical infections or activation of endogenous retroviruses 143 may be critical. While external environmental factors have been elusive in ALS, there is new interest in the intrinsic environment represented by the microbiome.…”

Section: Looking Forwardmentioning

confidence: 99%

Decoding ALS: from genes to mechanism

Taylor

Brown

Cleveland

2016

Nature

Self Cite

1,631

1,555

View full text Add to dashboard Cite

Preface Amyotrophic lateral sclerosis (ALS) is a progressive and uniformly fatal neurodegenerative disease. A plethora of genetic factors underlying ALS have now been identified that drive motor neuron degeneration, increase susceptibility to the disease, or influence the rate of progression. Emerging themes include dysfunction in RNA metabolism and protein homeostasis, with specific defects in nucleocytoplasmic trafficking, induction of endoplasmic reticulum stress, and impaired dynamics of ribonucleoprotein bodies such as RNA granules that assemble through the process of liquid-liquid phase separation. Extraordinary recent progress in understanding the biology of ALS provides new grounds for optimism that meaningful therapies for ALS will be identified.

show abstract

Section: Looking Forwardmentioning

confidence: 99%

Decoding ALS: from genes to mechanism

Taylor

Brown

Cleveland

2016

Nature

Self Cite

1,631

1,555

View full text Add to dashboard Cite

show abstract

“…The bulk of the genetic determinants of sALS remains elusive, and it is believed that exogenous environmental factors can activate endogenous retroviruses to initiate neurodegenerative changes ( Brown and Al-Chalabi 2015 ). Studies have reported some key features of ALS pathology, such as the involvement of mutated genes encoding RNA-binding proteins including the TARDBP ( Sreedharan et al, 2008 ), fused in sarcoma (FUS) ( Vance et al, 2009 ), and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) ( Kim et al, 2013 ).…”

Section: Amyotrophic Lateral Sclerosis Pathologymentioning

confidence: 99%

Potential of Cellular Therapy for ALS: Current Strategies and Future Prospects

Lin

Cheng

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive upper and lower motor neuron (MN) degeneration with unclear pathology. The worldwide prevalence of ALS is approximately 4.42 per 100,000 populations, and death occurs within 3–5 years after diagnosis. However, no effective therapeutic modality for ALS is currently available. In recent years, cellular therapy has shown considerable therapeutic potential because it exerts immunomodulatory effects and protects the MN circuit. However, the safety and efficacy of cellular therapy in ALS are still under debate. In this review, we summarize the current progress in cellular therapy for ALS. The underlying mechanism, current clinical trials, and the pros and cons of cellular therapy using different types of cell are discussed. In addition, clinical studies of mesenchymal stem cells (MSCs) in ALS are highlighted. The summarized findings of this review can facilitate the future clinical application of precision medicine using cellular therapy in ALS.

show abstract

“…In contrast, it remains unknown whether vertebrate hosts can exploit conserved PCD pathways in eukaryotic pathogens to affect infectious outcomes and maintain barrier immunity. Humans inhale ~10 3 to 10 10 mold conidia (i.e., vegetative spores) daily and, among these, Aspergillus fumigatus represents the most common agent of mold pneumonia worldwide (3). Sterilizing immunity depends on rapid conidial clearance by the respiratory immune system, primarily by neutrophils, macrophages, and monocytes (4–6), to prevent the formation of multicellular, tissue-invasive hyphae.…”

mentioning

confidence: 99%

Sterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death

Irmer

Dhingra

Beattie

et al. 2017

Science

View full text Add to dashboard Cite

Humans inhale mold conidia daily and typically experience lifelong asymptomatic clearance. Conidial germination into tissue-invasive hyphae can occur in individuals with defects in myeloid function, although the mechanism of myeloid cell–mediated immune surveillance remains unclear. By monitoring fungal physiology in vivo, we demonstrate that lung neutrophils trigger programmed cell death with apoptosis-like features in Aspergillus fumigatus conidia, the most prevalent human mold pathogen. An antiapoptotic protein, AfBIR1, opposes this process by inhibiting fungal caspase activation and DNA fragmentation in the murine lung. Genetic and pharmacologic studies indicate that AfBIR1 expression and activity underlie conidial susceptibility to NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-dependent killing and, in turn, host susceptibility to invasive aspergillosis. Immune surveillance exploits a fungal apoptosis-like programmed cell death pathway to maintain sterilizing immunity in the lung.

show abstract

Endogenous retroviruses in ALS: A reawakening?

Abstract: New data incriminate the human endogenous retrovirus HERV-K in the pathogenesis of ALS and document that the HERV-K envelope protein can be neurotoxic (Li et al ., this issue).

Cited by 11 publications

References 10 publications

Decoding ALS: from genes to mechanism

Decoding ALS: from genes to mechanism

Potential of Cellular Therapy for ALS: Current Strategies and Future Prospects

Sterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death

Contact Info

Product

Resources

About