Supersaturated proteins in ALS
| Autor: | Alan J. Cone, Elliott Hayden, Shulin Ju |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Protein Folding SOD1 Biology Protein Aggregation Pathological Inclusion bodies 03 medical and health sciences chemistry.chemical_compound Protein Aggregates 0302 clinical medicine Superoxide Dismutase-1 Commentaries medicine Humans Amyotrophic lateral sclerosis Gene Genetics Inclusion Bodies Motor Neurons Multidisciplinary Genetic heterogeneity Superoxide Superoxide Dismutase Neurodegeneration Amyotrophic Lateral Sclerosis Proteins Brain medicine.disease DNA-Binding Proteins 030104 developmental biology Spinal Nerves chemistry Solubility PNAS Plus Spinal Cord Proteome Mutation RNA-Binding Protein FUS 030217 neurology & neurosurgery |
| Popis: | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by rapidly progressive degeneration of motor neurons in the brain and spinal cord. Although most forms of ALS are sporadic (sALS), ∼10% of cases are inherited in families (fALS). More than 50 ALS genes have been identified, with 16 of them unequivocally implicated in the pathogenesis (1). These genes function in a wide spectrum of cellular processes, which has posed a considerable challenge in understanding common genetic causes of ALS. Another major question in ALS, and neurodegeneration in general, is related to the selectivity of neuronal cell death. Why is toxicity of mutant genes detrimental to certain types of neuronal cells, while leaving others unaffected? In the case of ALS, motor neurons are selectively degenerated. In PNAS, Ciryam et al. (2) investigate the expression level relative to protein solubility for ALS-associated proteins. Their results indicate that these proteins, compared with the whole proteome, are “supersaturated.” Furthermore, coaggregating proteins in inclusion bodies appear to be significantly more supersaturated in motor neurons than in other tissue types. These findings provide a plausible explanation for two aspects of ALS pathology: genetic heterogeneity and motor neuron-specific toxicity. One of the biggest breakthroughs in ALS research has been the identification of mutations in ALS-causing genes. The first gene linked to ALS was SOD1 in 1993 (3). SOD1 encodes a cytosolic Cu/Zn superoxide dismutase that catalyzes the dismutation of toxic superoxide anion to oxygen and hydrogen peroxide. Mutations in SOD1 account for ∼20% of fALS cases. The … [↵][1]1To whom correspondence should be addressed. Email: shulin.ju{at}wright.edu. [1]: #xref-corresp-1-1 |
| Databáze: | OpenAIRE |
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