scholarly journals IMMUNOHISTOCHEMICAL DEMONSTRATION OF Cu/Zn SUPEROXIDE DISMUTASE IN THE SPINAL CORD OF PATIENTS WITH FAMILIAL AMYOTRO-PHIC LATERAL SCLEROSIS

1993 ◽  
Vol 26 (6) ◽  
pp. 619-624 ◽  
Author(s):  
NORIYUKI SHIBATA ◽  
ASAO HIRANO ◽  
MAKIO KOBAYASHI ◽  
KOHTARO ASAYAMA ◽  
TAKAHIKO UMAHARA ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Superoxide Dismutase ◽  
Immunohistochemical Demonstration ◽  
Lateral Sclerosis

Voltage-Dependent Sodium Channels in Spinal Cord Motor Neurons Display Rapid Recovery From Fast Inactivation in a Mouse Model of Amyotrophic Lateral Sclerosis

2006 ◽  
Vol 96 (6) ◽  
pp. 3314-3322 ◽  
Author(s):  
Cristina Zona ◽  
Massimo Pieri ◽  
Irene Carunchio
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Mouse Model ◽  
Sodium Channels ◽  
Motor Neurons ◽  
Fast Inactivation ◽  
Patch Clamp Recording ◽  
Voltage Dependent ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a substantial loss of motor neurons in the spinal cord, brain stem, and motor cortex. Previous evidence showed that in a mouse model of a familial form of ALS expressing high levels of the human mutated protein Cu,Zn superoxide dismutase (Gly93→Ala, G93A), the firing properties of single motor neurons are altered to induce neuronal hyperexcitability. To determine whether the functionality of the macroscopic voltage-dependent Na+ currents is modified in G93A motor neurons, in the present work their physiological properties were examined. The voltage-dependent sodium channels were studied in dissociated motor neurons in culture from nontransgenic mice (Control), from transgenic mice expressing high levels of the human wild-type protein [superoxide dismutase 1 (SOD1)], and from G93A mice, using the whole cell configuration of the patch-clamp recording technique. The voltage dependency of activation and of steady-state inactivation, the kinetics of fast inactivation and slow inactivation of the voltage-dependent Na+ channels were not modified in the mutated mice. Conversely, the recovery from fast inactivation was significantly faster in G93A motor neurons than that in Control and SOD1. The recovery from fast inactivation was still significantly faster in G93A motor neurons exposed for different times (3–48 h) and concentrations (5–500 μM) to edaravone, a free-radical scavenger. Clarification of the importance of these changes in membrane ion channel functionality may have diagnostic and therapeutic implications in the pathogenesis of ALS.

Role of transition metals in the pathogenesis of amyotrophic lateral sclerosis

2008 ◽  
Vol 36 (6) ◽  
pp. 1322-1328 ◽  
Author(s):  
Willianne I.M. Vonk ◽  
Leo W.J. Klomp
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Transition Metals ◽  
Motor Neurons ◽  
Neurodegenerative Disorder ◽  
Sod1 Gene ◽  
Brain And Spinal Cord ◽  
Lateral Sclerosis

ALS (amyotrophic lateral sclerosis) is a devastating progressive neurodegenerative disorder resulting in selective degeneration of motor neurons in brain and spinal cord and muscle atrophy. In approx. 2% of all cases, the disease is caused by a mutation in the Cu,Zn-superoxide dismutase (SOD1) gene. The transition metals zinc and copper regulate SOD1 protein stability and activity, and disbalance of the homoeostasis of these metals has therefore been implicated in the pathogenesis of ALS. Recent data strengthen the hypothesis that these transition metals are excellent potential targets to develop an effective therapy for ALS.

Decrease in and Mn-superoxide dismutase activities in brain and spinal cord of patients with amyotrophic lateral sclerosis

1994 ◽  
Vol 127 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Makoto Uchino ◽  
Yukio Ando ◽  
Yoshiya Tanaka ◽  
Tetsuji Nakamura ◽  
Ei-ichiro Uyama ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Brain And Spinal Cord ◽  
Lateral Sclerosis

scholarly journals Impaired Cu-Zn superoxide dismutase (SOD1) and calcineurin (Cn) interaction in ALS: A presumed consequence for TDP-43 and zinc aggregation in Tg SOD1G93A rodent spinal cord tissue

2017 ◽  
Author(s):  
Jolene M. Kim ◽  
Elizabeth Billington ◽  
Ada Reyes ◽  
Tara Notarianni ◽  
Jessica Sage ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Animal Models ◽  
Protein Aggregation ◽  
Phosphatase Activity ◽  
Spinal Cord Tissue ◽  
Protein Levels ◽  
Tissue Homogenates ◽  
Lateral Sclerosis

ABSTRACTImpaired interactions between Calcineurin (Cn) and (Cu/Zn) superoxide dismutase (SOD1) are suspected to be responsible for the formation of hyperphosphorylated protein aggregation in amyotrophic lateral sclerosis (ALS). Serine (Ser)-enriched TDP-43 protein aggregation appears in the spinal cord of ALS animal models, and may be linked to the reduced phosphatase activity of Cn. The mutant overexpressed SOD1G93A protein does not properly bind zinc (Zn) in animal models; hence, mutant SOD1G93A - Cn interaction weakens. Consequently, unstable Cn fails to dephosphorylate TDP-43 that yields hyperphosphorylated TDP-43 aggregates. Our previous studies had suggested that Cn and SOD1 interaction was necessary to keep Cn enzyme functional. We have observed low Cn level, increased Zn concentrations, and increased TDP-43 protein levels in cervical, thoracic, lumbar, and sacral regions of the spinal cord tissue homogenates. This study further supports our previous published work indicating that Cn stability depends on functional Cn-SOD1 interaction because Zn metal is crucial for maintaining the Cn stability. Less active Cn did not efficiently dephosphorylate TDP-43; hence TDP-43 aggregations appeared in the spinal cord tissue.

scholarly journals Mutant superoxide dismutase aggregates from human spinal cord transmit amyotrophic lateral sclerosis

2018 ◽  
Vol 136 (6) ◽  
pp. 939-953 ◽  
Author(s):  
Elaheh Ekhtiari Bidhendi ◽  
Johan Bergh ◽  
Per Zetterström ◽  
Karin Forsberg ◽  
Bente Pakkenberg ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Human Spinal Cord ◽  
Lateral Sclerosis
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