ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein composition and decreases protein import.

Mutations in superoxide dismutase 1 (SOD1) cause familial ALS. Mutant SOD1 preferentially associates with the cytoplasmic face of mitochondria from spinal cords of rats and mice expressing SOD1 mutations. Two-dimensional gels and multidimensional liquid chromatography, in combination with tandem mass spectrometry, revealed 33 proteins that were increased and 21 proteins that were decreased in SOD1(G93A) rat spinal cord mitochondria compared with SOD1(WT) spinal cord mitochondria. Analysis of this group of proteins revealed a higher-than-expected proportion involved in complex I and protein import pathways. Direct import assays revealed a 30% decrease in protein import only in spinal cord mitochondria, despite an increase in the mitochondrial import components TOM20, TOM22, and TOM40. Recombinant SOD1(G93A) or SOD1(G85R), but not SOD1(WT) or a Parkinson's disease-causing, misfolded α-synuclein(E46K) mutant, decreased protein import by >50% in nontransgenic mitochondria from spinal cord, but not from liver. Thus, altered mitochondrial protein content accompanied by selective decreases in protein import into spinal cord mitochondria comprises part of the mitochondrial damage arising from mutant SOD1.

Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis.

Dominant mutations in superoxide dismutase cause amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease that is characterized by the loss of motor neurons. Using mice carrying a deletable mutant gene, diminished mutant expression in astrocytes did not affect onset, but delayed microglial activation and sharply slowed later disease progression. These findings demonstrate that mutant astrocytes are viable targets for therapies for slowing the progression of non-cell autonomous killing of motor neurons in ALS.

Progressive spinal axonal degeneration and slowness in ALS2-deficient mice.

OBJECTIVE: Homozygous mutation in the ALS2 gene and the resulting loss of the guanine exchange factor activity of the ALS2 protein is causative for autosomal recessive early-onset motor neuron disease that is thought to predominantly affect upper motor neurons. The goal of this study was to elucidate how the motor system is affected by the deletion of ALS2. METHODS: ALS2-deficient mice were generated by gene targeting. Motor function and upper and lower motor neuron pathology were examined in ALS2-deficient mice and in mutant superoxide dismutase 1 (SOD1) mice that develop ALS-like disease from expression of an ALS-linked mutation in SOD1. RESULTS: ALS2-deficient mice demonstrated progressive axonal degeneration in the lateral spinal cord that is also prominent in mutant SOD1 mice. Despite the vulnerability of these spinal axons, lower motor neurons in ALS2-deficient mice were preserved. Behavioral studies demonstrated slowed movement without muscle weakness in ALS2(-/-) mice, consistent with upper motor neuron defects that lead to spasticity in humans. INTERPRETATION: The combined evidence from mice and humans shows that deficiency in ALS2 causes an upper motor neuron disease that in humans closely resembles a severe form of hereditary spastic paralysis, and that is quite distinct from amyotrophic lateral sclerosis.

A Comparative Study of the Prolonged Effect with Neurectomy & Botox Injection Method on the Gastrocnemius Muscle Hypertrophy

PURPOSE: There was no controlled study on botox injection and neurectomy for treatments of muscle hypertrophy. Although many studies have shown the clinical effects of each treatment, it was not able to evaluate and compare the effects of each treatment because there was no comparison of the two treatments under the same experimental condition. Hence, the aim of this study is to com METHODS: The study was carried out on 21 rabbits. 9 rabbits received botox injection(botox injection group), and neurectomy was performed to another 9 rabbits (neurectomy group). 3 rabbits did not receive any treatment(control group). To compare and analyze the effects of muscular atrophy, muscle was stained with NADH-TR, and the changes in size of the muscle fiber were examined. And the electromyography was examined. In each group, muscle fiber was stained and electromyography was performed 2, 3, and 6 months after injection or operation. RESULTS: In histological test and electromyography, in the neurectomy group, the size of muscular fiber and amplitude of electromyography decreased until 2 months after neurectomy. And decreased results were maintained with the passage of time. It showed irreversible aspect. On the other hand, in the botox injection group, the decrease in the size of muscular fiber and amplitude of electromyography was observed until 2 months after injection. In 3 months after the injection, it was slowly getting back to original size and had almost recovered by 6 months after the injection. It showed reversible aspect. CONCLUSION: This study shows researches about clinical effect of botox injection and neurectomy coincide with the results of experiment under the same experimental condition.

Case Report of Recurrent Osteoma at the Grafted Bone

Surgical curettage or en bloc excision are the usual choice of treatment for osteoma. Local recurrence of osteoma after surgical treatment is not very common. We report a case of osteoma recurred at the grafted bone. A 5 x 8 cm sized osteoma of frontal bone was excised and then the defect was covered with calvarian bone and rib bone. Six years after reconstruction, recurrence from grafted area was noted. We completely removed the osteoma with enough normal tissue around it, after checking that the grafted bone has changed into an osteoma through a bicoronal incision. Then we covered the defect with a rib bone. The tissue was confirmed histologically as an osteoma. The recurrence of the tumor at the bone grafted site after osteoma excision is probably due to the fact that we covered grafted bone with periosteum left over osteoma. Therefore, we can learn that when we excise osteoma, galea should be carefully separated from the periphery of the tumor and that the periosteum should be completely removed, to prevent the osteoma from recurrence.

Clinical Experience of Maxillary Fibrous Dysplasia: Shaving, Partial Maxillectomy & Maxillary Sinus Formation

Fibrous dysplasia(FD) of the bone is a slowly progressive, benign disease of unknown cause where normal architectures are replaced with fibrous and osteoid tissue. FD of the maxilla usually manifests as a bony enlargement with painless swelling and bone deformity, contouring to facial asymmetry. The lesion may involve the nasal fossae, orbits, or alveolus bone, causing diverse functional disturbance. Treatment options range from shaving to total maxillectomy and reconstruction depending on the presenting symptoms. Shaving, partial maxillectomy and maxillary sinus formation was performed in 5 patients with fibrous dysplasia in the past 2 years. Follow up period ranged from 1 month to 11 months. Aesthetic appearance, CT findings, and relief from symptoms were compared. In all patients, facial asymmetry was restored to symmetry and nasal obstructive symptoms were improved. With this procedure, expansion of the lesion will be controlled until puberty, preventing the development of new functional disturbances. After puberty, no further treatment can be anticipated due to the growth arrest inherent to the disease.