Bunina bodies in amyotrophic lateral sclerosis immunostained with rabbit anti-cystatin C serum

Okamoto, Koichi; Hirai, Shunsaku; Amari, Masakuni; Watanabe, Mitsunori; Sakurai, Atsushi

doi:10.1016/0304-3940(93)90576-7

Cited by 116 publications

(82 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The neuropathology of ALS is characterized by the presence of various forms of inclusion bodies in degenerating neurons and surrounding reactive astrocytes [39]. "Skeinlike inclusions" (SLIs) [40,41] and Bunina bodies (BBs), which are cystatin C-containing inclusions in the cell bodies [42,43], are typical inclusions found in motor neurons in ALS. Tar DNA-binding protein 43 (TDP-43) is also localized in cytoplasmic ubiquitinated inclusions in sALS patient brains.…”

Section: Discussionmentioning

confidence: 99%

Species-dependent neuropathology in transgenic SOD1 pigs

Yang

Wang

Sun³

et al. 2014

Cell Res

View full text Add to dashboard Cite

Mutations in the human copper/zinc superoxide dismutase 1 (hSOD1) gene cause familial amyotrophic lateral sclerosis (ALS). It remains unknown whether large animal models of ALS mimic more pathological events seen in ALS patients via novel mechanisms. Here, we report the generation of transgenic pigs expressing mutant G93A hSOD1 and showing hind limb motor defects, which are germline transmissible, and motor neuron degeneration in dose-and age-dependent manners. Importantly, in the early disease stage, mutant hSOD1 did not form cytoplasmic inclusions, but showed nuclear accumulation and ubiquitinated nuclear aggregates, as seen in some ALS patient brains, but not in transgenic ALS mouse models. Our findings revealed that SOD1 binds PCBP1, a nuclear poly(rC) binding protein, in pig brain, but not in mouse brain, suggesting that the SOD1-PCBP1 interaction accounts for nuclear SOD1 accumulation and that species-specific targets are key to ALS pathology in large mammals and in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Species-dependent neuropathology in transgenic SOD1 pigs

Yang

Wang

Sun³

et al. 2014

Cell Res

View full text Add to dashboard Cite

show abstract

“…Changes in mRNA and protein expression of CYSC have been associated with oxidative stress [26]. Furthermore, changes in CYSC expression have been seen in various models of neuronal injuries such as PD [27][28][29], AD [30,31], ALS [32,33], heritable cerebral hemorrhage with amyloidosis of the Icelandic type angiopathy (HCHWA-I) [34], and transient forebrain ischemia [35]. However, the significance between the association of CYSC with CATB and CATD in neurodegenerative disorders and neuronal injury remains unknown.…”

Section: Introductionmentioning

confidence: 98%

Hydrogen Peroxide Induces Lysosomal Protease Alterations in PC12 Cells

et al. 2007

View full text Add to dashboard Cite

Alterations in lysosomal proteases have been implicated in many neurodegenerative diseases. The current study demonstrates a concentration-dependent decrease in PC12 cell viability and transient changes in cystatin C (CYSC), cathepsin B (CATB), cathepsin D (CATD) and caspase-3 following exposure to H2O2. Furthermore, activation of CATD occurred following exposure to H2O2 and cysteine protease suppression, while inhibition of CATD with pepstatin A significantly improved cell viability. Additionally, significant PARP cleavage, suggestive of caspase-3-like activity, was observed following H2O2 exposure, while inhibition of caspase-3 significantly increased cell viability compared to H2O2 administration alone. Collectively, our data suggest that H2O2 induced cell death is regulated at least in part by caspase-3 and CATD. Furthermore, cysteine protease suppression increases CATD expression and activity. These studies provide insight for alternate pathways and potential therapeutic targets of cell death associated with oxidative stress and lysosomal protease alterations.

show abstract

“…Various studies conducted in ALS postmortem tissue in the early nineties found accumulations of intermediate filament proteins (hyperphosphorylated neurofilament subunits and peripherin) in hyaline conglomerate inclusions and axonal "spheroids" in spinal cord motoneurons (Corbo and Hays, 1992;Munoz et al, 1988;Sobue et al, 1990), and pyramidal cells of the motor cortex (Troost et al, 1992). Moreover, cystatin C-containing Bunina bodies are found in the cell bodies of motoneurons in ALS (Okamoto et al, 1993;Sasaki and Maruyama, 1994). Some breakdown products of abnormal proteins caused by oxidative stress called ubiquitinated inclusion bodies (UIBs), are also implied in the pathogenesis of ALS (Alves-Rodrigues et al, 1998).…”

Section: Cellular and Molecular Pathogenesis Of Alsmentioning

confidence: 99%

Lactate dyscrasia: a novel explanation for amyotrophic lateral sclerosis

Meethal

Atwood

2012

Neurobiology of Aging

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease) is a progressive debilitating neurodegenerative disease with no cure. We propose a novel molecular model for the pathogenesis of ALS that involves an adenosine triphosphate (ATP)-dependent muscle neuronal lactate shuttle (MNLS) at the neuromuscular junction (NMJ) to regulate the flow of lactate from muscle to neurons and vice versa. Failure of the MNLS due to respiratory chain dysfunction is proposed to result in lactate toxicity and degeneration of nerve endings at the NMJ leading to nerve terminus dysjunction from the muscle cell. At a critical threshold where denervation outpaces reinnervation, a vicious cycle is established where the remaining innervated muscle fibers are required to work harder to compensate for normal function, and in so doing produce toxic lactate concentrations which induces further denervation and neuronal death. This mechanism explains the exponential progression of ALS leading to paralysis. The molecular events leading to the dysregulation of the MNLS and the dismantling of NMJ are explained in the context of known ALS familial mutations and age-related endocrine dyscrasia. Combination drug therapies that inhibit lactate accumulation at the NMJ, enhance respiratory chain function, and/or promote reinnervation are predicted to be effective therapeutic strategies for ALS. Published by Elsevier Inc.

show abstract

Bunina bodies in amyotrophic lateral sclerosis immunostained with rabbit anti-cystatin C serum

Cited by 116 publications

References 11 publications

Species-dependent neuropathology in transgenic SOD1 pigs

Species-dependent neuropathology in transgenic SOD1 pigs

Hydrogen Peroxide Induces Lysosomal Protease Alterations in PC12 Cells

Lactate dyscrasia: a novel explanation for amyotrophic lateral sclerosis

Contact Info

Product

Resources

About