Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death

By M. Arrasate, S. Mitra, E. Schweitzer, Mark R. Segal, S. Finkbeiner. Nature, 2004

2,062 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6c5874fb2e5bbe81c7f630bd2fbb0266a291005e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. L. Mucke
2. J. Palop
3. N. Mizushima
4. D. Selkoe
5. M. Komatsu
6. D. Klionsky
7. Christian Haass
8. C. Zuccato

In Molecular Biology

1. N. Mizushima
2. D. Klionsky
3. M. Komatsu
4. D. Rubinsztein
5. Masayuki Yamamoto
6. P. Muchowski
7. D. Selkoe
8. E. Kominami

Citations in the corpus

• Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide (2007, background): “For example, in cell-culture studies of HD, less cell death has been observed when large aggregates of polyglutamine-rich huntingtin protein are present in the cells than when only soluble huntingtin is present without these inclusion”
• Pathways of cellular proteostasis in aging and disease (2018, background): “Although the exact nature of the most-toxic species remains a subject of discussion, in many cases the larger amyloid aggregates may exert a relative protective effect by sequestering the more-toxic oligomers and by having a reduced surface-to-volume ratio (Saudou et al., 1998; Arrasate et al., 2004”
• Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein (2017, methodology): “Accumulation of mHtt triggers a variety of insults that lead to striatal degeneration, however, the nature of the specific mHtt species, soluble, oligomeric or aggregate, that triggers neurodegeneration remains unclear (Arrasate et al., 2004; Lajoie and Snapp, 2010).”
• Widespread Protein Aggregation as an Inherent Part of Aging in C. elegans (2010, background): “Why might this be? Many recent studies show that low-MW oligomers formed by diseasemisfolded proteins are at least as, if not more, toxic as high-MW, visible, aggregates [43,84,85,86].”
• Diseases of Unstable Repeat Expansion: Mechanisms and Common Principles (2005, background): “These include SCA1 and SCA7 knockin mice and a cell-based assa”
• Modulation of neurodegeneration by molecular chaperones (2005, background): “, which showed that in a cell culture model of HD, inclusion body formation predicts neuronal survival, whereas the level of diffuse huntingtin correlates significantly with cell deat”
• Protein Phase Separation: A New Phase in Cell Biology (2018, background): “Second, although protein aggregates in disease are considered harmful, accumulating evidence suggests that they could be an initial rescue mechanism of the cell to sequester the more toxic protein oligomers [149,150].”
• Autophagy and apoptosis dysfunction in neurodegenerative disorders. (2014, neutral): “On the other hand, there are studies suggesting that aggregates themselves might actually serve a neuroprotective function (Arrasate et al., 2004; Rubinsztein, 2006).”
• Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. (2007, background): “However, emerging evidence indicates that protein aggregates containing disease-related proteins (e.g., polyQ) can provide protection (Arrasate et al., 2004; Ross and Poirier, 2005; Sanchez et al., 2003).”