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… 
View on Wolters Kluwer
ncbi.nlm.nih.gov
102 Citations
Highly Influential Citations
2
Background Citations
16
Results Citations
1

102 Citations

Familial amyotrophic lateral sclerosis
TLDR
There has become evident that there is considerable interplay between these mechanisms and, as the role of each is established, a common picture may emerge, enabling the development of more targeted therapies.
Amyotrophic lateral sclerosis.
Kennedy’s disease: a triplet repeat disorder or a motor neuron disease?
  • J. Gallo
  • Biology
    Brain Research Bulletin
  • 2001
Pathophysiology of Amyotrophic Lateral Sclerosis
TLDR
There is an explosion of genetic studies associating ALS with several genetic mutations in genes codifying for different proteins: Cu/Zn superoxide dismutase, SOD1, transactive response binding protein 43 (TARDBP), fused in sarcoma (FUS), and valosin containing protein (VCP).
Homocysteine levels and amyotrophic lateral sclerosis: A possible link
TLDR
Several types of evidence show that accumulation of Hcy may increase the risk and progression of motoneuronal degeneration and, if confirmed, early interventions to decrease Hcy levels may be useful to modify ALS progression and possibly onset.
Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1G93A transgenic mice
Amyotrophic lateral sclerosis: clinical perspectives
TLDR
The most important approach to improve the patient's quality of life remains symptom-based management, and this review gives an overview of the current treatment offered in multidisciplinary clinics.
Expression of peripherin in ubiquinated inclusions of amyotrophic lateral sclerosis
  • C. HeA. Hays
  • Biology
    Journal of the Neurological Sciences
  • 2004
Protective effects of cardiotrophin-1 adenoviral gene transfer on neuromuscular degeneration in transgenic ALS mice.
TLDR
Monitoring the amplitude of the evoked motor response showed that the time-course of motor impairment was significantly decreased by CT-1 treatment, suggesting adenovirus-mediated gene transfer of neurotrophic factors might delay neurogenic muscular atrophy and progressive neuromuscular deficiency in ALS patients.
A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q.
TLDR
Haplotype analysis has identified a 7.5-cM, 8-Mb region of chromosome 18q21, flanked by markers D 18S846 and D18S1109, as a novel FALS locus, a novel locus identified by performing a genome scan and linkage analysis.
...
...

References

SHOWING 1-10 OF 84 REFERENCES
Aberrant RNA Processing in a Neurodegenerative Disease: the Cause for Absent EAAT2, a Glutamate Transporter, in Amyotrophic Lateral Sclerosis
Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis.
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.
Analysis of chromosome 5q13 genes in amyotrophic lateral sclerosis: Homozygous naip deletion in a sporadic case
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.
SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter
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.
Lack of involvement of neuronal nitric oxide synthase in the pathogenesis of a transgenic mouse model of familial amyotrophic lateral sclerosis
Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis.
TLDR
Analysis of samples from two different populations and four novel NFH tail deletions, each involving a whole motif, strongly suggest that NFH motif deletions can be a primary event in ALS but that they are not common.
Mitochondrial enzyme activity in amyotrophic lateral sclerosis: Implications for the role of mitochondria in neuronal cell death
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.
Splicing of the glutamate transporter EAAT2: a candidate gene of amyotrophic lateral sclerosis
TLDR
In vitro expression studies suggested that proteins translated from these transcripts were rapidly degraded and show a dominant negative effect on normal EAAT2 protein which appears to be the predominat glutamate transporter protein.
Inducible Nitric Oxide Synthase Up‐Regulation in a Transgenic Mouse Model of Familial Amyotrophic Lateral Sclerosis
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.
The relationship of spinal muscular atrophy to motor neuron disease: Investigation of SMN and NAIP gene deletions in sporadic and familial ALS
...
...