Share This Author
Amyotrophic Lateral Sclerosis-Associated SOD1 Mutant Proteins Bind and Aggregate with Bcl-2 in Spinal Cord Mitochondria
Antisense Proline-Arginine RAN Dipeptides Linked to C9ORF72-ALS/FTD Form Toxic Nuclear Aggregates that Initiate In Vitro and In Vivo Neuronal Death
Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons
An intronic GGGGCC repeat expansion in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the pathogenic mechanism of this repeat remains…
Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration?
An over-oxidized form of superoxide dismutase found in sporadic amyotrophic lateral sclerosis with bulbar onset shares a toxic mechanism with mutant SOD1
- S. Guareschi, E. Cova, P. Pasinelli
- BiologyProceedings of the National Academy of Sciences
- 13 March 2012
It is shown here that indeed WT SOD1 is modified posttranslationally in sporadic ALS and is iper-oxidized (i.e., above baseline oxidation levels) in a subset of patients with bulbar onset, providing an opportunity to develop biomarkers to subclassify ALS and devise S OD1-based therapies that go beyond the small group of Patients with mutant SOD 1.
SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter
- D. Trotti, A. Rolfs, N. Danbolt, Robert H. Brown, M. Hediger
- Biology, ChemistryNature Neuroscience
- 1 May 1999
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.
Cloning and characterization of a potassium-coupled amino acid transporter.
- M. Castagna, C. Shayakul, D. Trotti, V. Sacchi, W. Harvey, M. Hediger
- BiologyProceedings of the National Academy of Sciences…
- 28 April 1998
The present work extends the Na+ and H+ dogma by including the H+ and K+ paradigm and isolated a cDNA that encodes a K+-coupled amino acid transporter (KAAT1), reflecting the increased K+/Na+ selectivity with hyperpolarization observed in midgut tissue.
ALS-linked mutant SOD1 damages mitochondria by promoting conformational changes in Bcl-2
The identification of Bcl-2 as a specific target and active partner in mutant SOD1 mitochondrial toxicity suggests new therapeutic strategies to inhibit the formation of the toxic mutant S OD1/B cl-2 complex and to prevent mitochondrial damage in ALS.
Caspase-3 Cleaves and Inactivates the Glutamate Transporter EAAT2*
- William Boston-Howes, Stuart L. Gibb, Eric O. Williams, P. Pasinelli, Robert H. Brown, D. Trotti
- BiologyJournal of Biological Chemistry
- 19 May 2006
The novel evidence that caspase-3 cleaves EAAT2 at a unique site located in the cytosolic C-terminal domain of the transporter is reported, a finding that links excitotoxicity and activation of caspases as converging mechanisms in the pathogenesis of ALS.
Glutamate uptake inhibition by oxygen free radicals in rat cortical astrocytes
- A. Volterra, D. Trotti, C. Tromba, S. Floridi, G. Racagni
- BiologyThe Journal of neuroscience : the official…
- 1 May 1994
Data suggest that free radicals inhibit glutamate uptake primarily by long-lasting oxidation of protein sulfhydryl (SH) groups, and chemical modifiers of free SH groups, such as p-chloromercuribenzoate and N-ethylmaleimide, also induce uptake inhibition.