Arylsulfanyl pyrazolones block mutant SOD1-G93A aggregation. Potential application for the treatment of amyotrophic lateral sclerosis

Arylsulfanyl pyrazolones block mutant SOD1-G93A aggregation. Potential application for the treatment of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease currently without a cure. Mutations in copper/zinc superoxide dismutase 1 (SOD1) have been implicated in the pathophysiology of this disease. Using a high-throughput screening assay expressing mutant G93A SOD1, two bioactive chemical hit compounds (1 and 2), identified as arylsulfanyl pyrazolones, were identified. The st...

Adaptive Immune Neuroprotection in G93A-SOD1 Amyotrophic Lateral Sclerosis Mice

BACKGROUND Innate neuroimmune dysfunction is a pathobiological feature of amyotrophic lateral sclerosis (ALS). However, links, if any, between disease and adaptive immunity are poorly understood. Thus, the role of T cell immunity in disease was investigated in human G93A superoxide dismutase 1 (SOD1) transgenic (Tg) mice and subsequently in ALS patients. METHODS AND FINDINGS Quantitative and ...

Identification of compounds protective against G93A-SOD1 toxicity for the treatment of amyotrophic lateral sclerosis.

The underlying cause of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disorder, remains unknown. However, there is strong evidence that one pathophysiological mechanism, toxic protein misfolding and/or aggregation, may trigger motor neuron dysfunction and loss. Since the clinical and pathological features of sporadic and familial ALS are indistinguishable, all forms of th...

Mutant Profilin1 Aggregation in Amyotrophic Lateral Sclerosis: An in Vivo Biochemical Analysis

Introduction: Profilin1 (PFN1) is a ubiquitously expressed protein known for its function as a regulator of actin polymerization and dynamics. A recent discovery linked mutant PFN1 to Amyotrophic Lateral Sclerosis (ALS), which is a fatal and progressive motor neuron disease. We have also demonstrated that Gly118Val mutation in PFN1 is a cause of ALS, and the formation of aggregates containing m...

The neuromuscular transmission of the SOD1(G93A) mouse model of Amyotrophic Lateral Sclerosis