Amyotrophic Lateral Sclerosis

Publication Title: 
Free Radical Biology & Medicine

Mutations in human CuZn superoxide dismutase (SOD) have been associated with familial amyotrophic lateral sclerosis (FALS). Although leading to many experimental advances, this finding has not yet led to a clear understanding of the biochemical mechanism by which mutations in SOD promote the degeneration of motorneurons that causes this incurable paralytic disease.

Author(s): 
Elia, A. J.
Parkes, T. L.
Kirby, K.
St George-Hyslop, P.
Boulianne, G. L.
Phillips, J. P.
Hilliker, A. J.
Publication Title: 
Journal of the Neurological Sciences

Amyotrophic lateral sclerosis (ALS) is a progressive disease which is caused by degeneration of motor neurons in the central nervous system. The incidence of ALS is higher in men than women, but the female advantage disappears with increased age. Here, we report evidence that the female advantage is due to the protective role of estrogen. In an ALS mouse model carrying the human Cu/Zn superoxide dismutase (hSOD1) G93A transgene, ovariectomy did not alter the onset age of the disease while reducing the female lifespan by 7 days and making it comparable to that of the male transgenic mice.

Author(s): 
Choi, Chan-Il
Lee, Young-Don
Gwag, Byoung Joo
Cho, Sung Ig
Kim, Sung-Soo
Suh-Kim, Haeyoung
Publication Title: 
Experimental & Molecular Medicine

Neural progenitor cells (NPs) have shown several promising benefits for the treatment of neurological disorders. To evaluate the therapeutic potential of human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1(G93A)) transgenic mice.

Author(s): 
Park, Sungju
Kim, Hyoung-Tae
Yun, Seokkwan
Kim, Il-Sun
Lee, Jiyoon
Lee, Il-Shin
Park, Kook In
Publication Title: 
CNS neuroscience & therapeutics

Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease of adults which preferentially attacks the neuromotor system. Riluzole has been used as the only approved treatment for amyotrophic lateral sclerosis since 1995, but its mechanism(s) of action in slowing the progression of this disease remain obscure. Searching PubMed for "riluzole" found 705 articles published between January 1996 and June 2009.

Author(s): 
Bellingham, Mark C.
Publication Title: 
PloS One

BACKGROUND: Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the lumbar spinal cord of SOD1(G93A) rats leads to a moderate therapeutical effect as evidenced by local ?-motoneuron sparing and extension of lifespan.

Author(s): 
Hefferan, Michael P.
Galik, Jan
Kakinohana, Osamu
Sekerkova, Gabriela
Santucci, Camila
Marsala, Silvia
Navarro, Roman
Hruska-Plochan, Marian
Johe, Karl
Feldman, Eva
Cleveland, Don W.
Marsala, Martin
Publication Title: 
Human Molecular Genetics

In amyotrophic lateral sclerosis (ALS), the progressive loss of motor neurons is accompanied by extensive muscle denervation, resulting in paralysis and ultimately death. Upregulation of amyloid beta (A4) precursor protein (APP) in muscle fibres coincides with symptom onset in both sporadic ALS patients and the SOD1(G93A) mouse model of familial ALS.

Author(s): 
Bryson, J. Barney
Hobbs, Carl
Parsons, Michael J.
Bosch, Karen D.
Pandraud, Amelie
Walsh, Frank S.
Doherty, Patrick
Greensmith, Linda
Publication Title: 
PLoS genetics

TDP-43 is a multifunctional nucleic acid binding protein linked to several neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia. To learn more about the normal biological and abnormal pathological role of this protein, we turned to Caenorhabditis elegans and its orthologue TDP-1. We report that TDP-1 functions in the Insulin/IGF pathway to regulate longevity and the oxidative stress response downstream from the forkhead transcription factor DAF-16/FOXO3a.

Author(s): 
Vaccaro, Alexandra
Tauffenberger, Arnaud
Ash, Peter E. A.
Carlomagno, Yari
Petrucelli, Leonard
Parker, J. Alex
Publication Title: 
Neuromolecular Medicine

A common cause of amyotrophic lateral sclerosis is mutations in superoxide dismutase-1, which provoke the disease by an unknown mechanism. We have previously found that soluble hydrophobic misfolded mutant human superoxide dismutase-1 species are enriched in the vulnerable spinal cords of transgenic model mice. The levels were broadly inversely correlated with life spans, suggesting involvement in the pathogenesis.

Author(s): 
Zetterstrˆm, Per
Graffmo, Karin S.
Andersen, Peter M.
Br‰nnstrˆm, Thomas
Marklund, Stefan L.
Publication Title: 
Cell Death and Differentiation

Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition with no cure. Mitochondrial dysfunction, Ca(2+) overloading and local hypoxic/ischemic environments have been implicated in the pathophysiology of ALS and are conditions that may initiate metabolic acidosis in the affected tissue. We tested the hypothesis that acidotoxicity and acid-sensing ion channels (ASICs) are involved in the pathophysiology of ALS. We found that motoneurons were selectively vulnerable to acidotoxicity in vitro, and that acidotoxicity was partially reduced in asic1a-deficient motoneuron cultures.

Author(s): 
Behan, A. T.
Breen, B.
Hogg, M.
Woods, I.
Coughlan, K.
Mitchem, M.
Prehn, J. H. M.
Publication Title: 
PloS One

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive paralysis due to motor neuron death. Several lines of published evidence suggested that inhibition of epidermal growth factor receptor (EGFR) signaling might protect neurons from degeneration. To test this hypothesis in vivo, we treated the SOD1 transgenic mouse model of ALS with erlotinib, an EGFR inhibitor clinically approved for oncology indications.

Author(s): 
Le Pichon, Claire E.
Dominguez, Sara L.
Solanoy, Hilda
Ngu, Hai
Lewin-Koh, Nicholas
Chen, Mark
Eastham-Anderson, Jeffrey
Watts, Ryan
Scearce-Levie, Kimberly

Pages

Subscribe to RSS - Amyotrophic Lateral Sclerosis