Updates on amyotrophic lateral sclerosis: Improving patient care

Bradley, Walter G.

doi:10.1002/ana.21546

Cited by 11 publications

(4 citation statements)

References 16 publications

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“…A myotrophic lateral sclerosis (ALS) is a progressive, fatal neuromuscular disease characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body (Cleveland and Rothstein 2001;Bradley 2009). The term "amyotrophic lateral sclerosis" was coined by the French neurologist Jean-Martin Charcot in the 1800s: "amyotrophic" refers to muscular atrophy, and "lateral sclerosis" describes the scarring or hardening of tissues in the lateral spinal cord.…”

mentioning

confidence: 99%

Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS)

Grad

Rouleau

Ravits

et al. 2016

Cold Spring Harb Perspect Med

207

137

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Amyotrophic lateral sclerosis (ALS) is primarily characterized by progressive loss of motor neurons, although there is marked phenotypic heterogeneity between cases. Typical, or "classical," ALS is associated with simultaneous upper motor neuron (UMN) and lower motor neuron (LMN) involvement at disease onset, whereas atypical forms, such as primary lateral sclerosis and progressive muscular atrophy, have early and predominant involvement in the UMN and LMN, respectively. The varying phenotypes can be so distinctive that they would seem to have differing biology. Because the same phenotypes can have multiple causes, including different gene mutations, there may be multiple molecular mechanisms causing ALS, implying that the disease is a syndrome. Conversely, multiple phenotypes can be caused by a single gene mutation; thus, a single molecular mechanism could be compatible with clinical heterogeneity. The pathogenic mechanism(s) in ALS remain unknown, but active propagation of the pathology neuroanatomically is likely a primary component.

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mentioning

confidence: 99%

Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS)

Grad

Rouleau

Ravits

et al. 2016

Cold Spring Harb Perspect Med

207

137

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“…Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by the loss of upper and lower motor neurons [1][2][3]. Approximately 10% of individuals with ALS have a family history, and Cu/Zn superoxide dismutase 1 (SOD1) was the first gene associated with ALS [4,5].…”

Section: Introductionmentioning

confidence: 99%

Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation

Hashimoto

Yamasaki

et al. 2022

IJMS

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Connexin 30 (Cx30), which forms gap junctions between astrocytes, regulates cell adhesion and migration, and modulates glutamate transport. Cx30 is upregulated on activated astroglia in central nervous system inflammatory lesions, including spinal cord lesions in mutant superoxide dismutase 1 (mSOD1) transgenic amyotrophic lateral sclerosis (ALS) model mice. Here, we investigated the role of Cx30 in mSOD1 mice. Cx30 was highly expressed in the pre-onset stage in mSOD1 mice. mSOD1 mice with knockout (KO) of the Cx30 gene (Cx30KO-mSOD1 mice) showed delayed disease onset and tended to have an extended survival period (log-rank, p = 0.09). At the progressive and end stages of the disease, anterior horn cells were significantly preserved in Cx30KO-mSOD1 mice. In lesions of these mice, glial fibrillary acidic protein/C3-positive inflammatory astroglia were decreased. Additionally, the activation of astrocytes in Cx30KO-mSOD1 mice was reduced compared with mSOD1 mice by gene expression microarray. Furthermore, expression of connexin 43 at the pre-onset stage was downregulated in Cx30KO-mSOD1 mice. These findings suggest that reduced expression of astroglial Cx30 at the early disease stage in ALS model mice protects neurons by attenuating astroglial inflammation.

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“…Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular condition characterized by degeneration of the upper and lower motor neurons causing progressive muscle paralysis and spasticity that affects mobility, speech, swallowing, and respiration. 1,2 Half of affected individuals die within 3 years and less than 20% survive for more than 5 years. 3 The etiology of ALS is unknown; however, similar to other neurodegenerative diseases such as Alzheimer disease and Creutzfeldt-Jakob disease, 90-95% of cases are sporadic in which some predisposing gene mutations have been identified, such as those encoding ataxin-2 repeat expansions.…”

Section: Introductionmentioning

confidence: 99%

Prion-like activity of Cu/Zn superoxide dismutase

Grad

Cashman

2014

Prion

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Neurodegenerative diseases belong to a larger group of protein misfolding disorders, known as proteinopathies. There is increasing experimental evidence implicating prion-like mechanisms in many common neurodegenerative disorders, including Alzheimer disease, Parkinson disease, the tauopathies, and amyotrophic lateral sclerosis (ALS), all of which feature the aberrant misfolding and aggregation of specific proteins. The prion paradigm provides a mechanism by which a mutant or wild-type protein can dominate pathogenesis through the initiation of self-propagating protein misfolding. ALS, a lethal disease characterized by progressive degeneration of motor neurons is understood as a classical proteinopathy; the disease is typified by the formation of inclusions consisting of aggregated protein within and around motor neurons that can contribute to neurotoxicity. It is well established that misfolded/oxidized SOD1 protein is highly toxic to motor neurons and plays a prominent role in the pathology of ALS. Recent work has identified propagated protein misfolding properties in both mutant and wild-type SOD1, which may provide the molecular basis for the clinically observed contiguous spread of the disease through the neuroaxis. In this review we examine the current state of knowledge regarding the prion-like properties of SOD1 and comment on its proposed mechanisms of intercellular transmission.

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Updates on amyotrophic lateral sclerosis: Improving patient care

Cited by 11 publications

References 16 publications

Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS)

Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS)

Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation

Prion-like activity of Cu/Zn superoxide dismutase

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