Recent advances in amyotrophic lateral sclerosis

@article{AlChalabi2000RecentAI,
  title={Recent advances in amyotrophic lateral sclerosis},
  author={Ammar Al-Chalabi and Peter Nigel Leigh},
  journal={Current Opinion in Neurology},
  year={2000},
  volume={13},
  pages={397-405}
}
The mechanisms by which mutations of the SOD1 gene cause selective motor neuron death remain uncertain, although interest continues to focus on the role of peroxynitrite, altered peroxidase activity of mutant SOD1, changes in intracellular copper homeostasis, protein aggregation, and changes in the function of glutamate transporters leading to excitotoxicity. Neurofilaments and peripherin appear to play some part in motor neuron degeneration, and amyotrophic lateral sclerosis is occasionally… 
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TLDR
It is proposed that changes in the KSP-repeat domain may affect the cross-linking properties of the heavy neurofilaments subunit and perhaps contribute to the development of neurofilamentous swellings in motor neurons, a hallmark of ALS.
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TLDR
The possibility of alterations in SMN and NAIP in 154 patients with ALS is investigated, and a single patient revealed a partial deletion of NAIP, which is possible that this individual is one of the rare carriers of SMA who show NAIP deletions.
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TLDR
It is proposed that toxic properties of S OD1 mutants lead to neuronal death via an excitotoxic mechanism in SOD1-linked FALS through oxidative reactions triggered by hydrogen peroxide and catalyzed by A4V and I113T mutant but not wild-type SOD 1 inactivated the glutamate transporter human GLT1.
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TLDR
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TLDR
There is a selective decrease in the activity of the mitochondrial DNA–encoded enzyme cytochrome c oxidase in human spinal cord motor neurons in sporadic ALS, and this may not only be important in neuronal cell death but could well be caused by oxidative damage to mitochondrial DNA leading to the accumulation of mitochondrial DNA mutations.
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TLDR
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TLDR
The observed alterations do not initiate the death of motor neurons, but may contribute to the propagation of the neurodegenerative process, and it is suggested that iNOS may represent a valuable target for the development of new therapeutic avenues for ALS.
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