Fine Structural Study of Neurofibrillary Changes in a Family with Amyotrophic Lateral Sclerosis

Hirano, Atsushi; Nakano, Imaharu; Kurland, Leonard T.; Mulder, Donald W.; Holley, P.; Saccomanno, Geno

doi:10.1097/00005072-198409000-00002

Cited by 282 publications

(140 citation statements)

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“…Neurodegeneration in the retinoid-deficient rat and motoneuron disease patients have a similar pathology In the motoneurons of the adult retinoid-deficient rat, there was an accumulation of neurofilament, vacuolations of the motoneurons and an increase in astrocytosis, which are all phenotypes observed in both human sporadic (Carpenter, 1968;Hirano et al, 1984a) and SOD1-mediated familial ALS (Hirano et al, 1984b;Rouleau et al, 1996;Shibata et al, 1996). This suggests that the motoneurons in both the rat and the human disease undergo a similar mechanism of Journal of Cell Science 115 (24) degeneration.…”

Section: Discussionmentioning

confidence: 88%

Absence of retinoids can induce motoneuron disease in the adult rat and a retinoid defect is present in motoneuron disease patients

Corcoran

Maden

2002

Journal of Cell Science

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We generated retinoid-deficient adult rats by the removal of retinoids from their diet. We show that their motoneurons undergo neurodegeneration and that there is an accumulation of neurofilaments and an increase in astrocytosis,which is associated with motoneuron disease. These effects are mediated through the retinoic acid receptor α. The same receptor deficit is found in motoneurons from patients suffering from spontaneous amyotrophic lateral sclerosis. Furthermore, we show that there is a loss of expression of the retinaldehyde dehydrogenase enzyme II in motoneurons. Therefore, we propose that a defect in the retinoid signalling pathway is in part be responsible for some types of motoneuron disease.

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Section: Discussionmentioning

confidence: 88%

Absence of retinoids can induce motoneuron disease in the adult rat and a retinoid defect is present in motoneuron disease patients

Corcoran

Maden

2002

Journal of Cell Science

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“…ALS patients and mice expressing mutant superoxide dismutase 1 (SOD1) display neurofilament accumulations, which may derive from defects in slow anterograde transport (19,24,25). Furthermore, alterations in fast axonal transport have been shown in embryonic SOD1 G93A MNs and inferred from postmortem human ALS axons (18,25,26).…”

mentioning

confidence: 99%

Deficits in axonal transport precede ALS symptoms in vivo

Bilsland¹,

Sahai

Kelly

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

359

343

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ALS is a fatal neurodegenerative disease characterized by selective motor neuron death resulting in muscle paralysis. Mutations in superoxide dismutase 1 (SOD1) are responsible for a subset of familial cases of ALS. Although evidence from transgenic mice expressing human mutant SOD1 G93A suggests that axonal transport defects may contribute to ALS pathogenesis, our understanding of how these relate to disease progression remains unclear. Using an in vivo assay that allows the characterization of axonal transport in single axons in the intact sciatic nerve, we have identified clear axonal transport deficits in presymptomatic mutant mice. An impairment of axonal retrograde transport may therefore represent one of the earliest axonal pathologies in SOD1 G93A mice, which worsens at an early symptomatic stage. A deficit in axonal transport may therefore be a key pathogenic event in ALS and an early disease indicator of motor neuron degeneration.

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“…A pathological hallmark of both sporadic and familial ALS involves the abnormal accumulation of cytoskeletal proteins such as neurofilament, tubulin, and actin in the perikaryon and axon of motor neurons (12,17,19,31). Recent studies have reported that these cytoskeletal changes induce slowing of axonal transport in mutated Cu,Zn-SOD transgenic mice (37).…”

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confidence: 99%

Overexpression of mutated Cu,Zn-SOD in neuroblastoma cells results in cytoskeletal change

Takamiya

Takahashi²,

Park³

et al. 2005

American Journal of Physiology-Cell Physiology

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Amyotrophic lateral sclerosis (ALS) involves the progressive degeneration of motor neurons in the spinal cord and the motor cortex. It has been shown that 15–20% of patients with familial ALS (FALS) have defects in the Sod1 gene, which encodes Cu,Zn-superoxide dismutase (SOD). To elucidate the pathological role of mutated Cu,Zn-SOD, we examined the issue of whether mutated Cu,Zn-SOD affects the cell cycle. Mouse neuroblastoma Neuro-2a cells were transfected with human wild-type or mutated (G37R, G93A) Cu,Zn-SOD. Mutated, Cu,Zn-SOD-transfected cells exhibited marked retardation in cell growth and G2/M arrest. They also displayed lower reactivity to phalloidin, indicating that the cytoskeleton was disrupted. Immunoprecipitation, two-dimensional gel electrophoresis, and Western blot analysis indicated that mutated Cu,Zn-SOD associates with actin. Similar results were obtained by in vitro incubation experiments with purified actin and mutated Cu,Zn-SOD (G93A). These results suggest that mutated Cu,Zn-SOD in FALS causes cytoskeletal changes by associating with actin, which subsequently causes G2/M arrest and growth retardation.

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Fine Structural Study of Neurofibrillary Changes in a Family with Amyotrophic Lateral Sclerosis

Cited by 282 publications

References 0 publications

Absence of retinoids can induce motoneuron disease in the adult rat and a retinoid defect is present in motoneuron disease patients

Absence of retinoids can induce motoneuron disease in the adult rat and a retinoid defect is present in motoneuron disease patients

Deficits in axonal transport precede ALS symptoms in vivo

Overexpression of mutated Cu,Zn-SOD in neuroblastoma cells results in cytoskeletal change

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