Title |
Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa
|
---|---|
Published in |
Scientific Reports, August 2014
|
DOI | 10.1038/srep05970 |
Pubmed ID | |
Authors |
Hanako Ohashi Ikeda, Norio Sasaoka, Masaaki Koike, Noriko Nakano, Yuki Muraoka, Yoshinobu Toda, Tomohiro Fuchigami, Toshiyuki Shudo, Ayana Iwata, Seiji Hori, Nagahisa Yoshimura, Akira Kakizuka |
Abstract |
Neuroprotection may prevent or forestall the progression of incurable eye diseases, such as retinitis pigmentosa, one of the major causes of adult blindness. Decreased cellular ATP levels may contribute to the pathology of this eye disease and other neurodegenerative diseases. Here we describe small compounds (Kyoto University Substances, KUSs) that were developed to inhibit the ATPase activity of VCP (valosin-containing protein), the most abundant soluble ATPase in the cell. Surprisingly, KUSs did not significantly impair reported cellular functions of VCP but nonetheless suppressed the VCP-dependent decrease of cellular ATP levels. Moreover, KUSs, as well as exogenous ATP or ATP-producing compounds, e.g. methylpyruvate, suppressed endoplasmic reticulum stress, and demonstrably protected various types of cultured cells from death, including several types of retinal neuronal cells. We then examined their in vivo efficacies in rd10, a mouse model of retinitis pigmentosa. KUSs prevented photoreceptor cell death and preserved visual function. These results reveal an unexpected, crucial role of ATP consumption by VCP in determining cell fate in this pathological context, and point to a promising new neuroprotective strategy for currently incurable retinitis pigmentosa. |
X Demographics
As of 1 July 2024, you may notice a temporary increase in the numbers of X profiles with Unknown location. Click here to learn more.
Geographical breakdown
Country | Count | As % |
---|---|---|
Japan | 3 | 38% |
Unknown | 5 | 63% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 8 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 54 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 11 | 20% |
Student > Ph. D. Student | 9 | 17% |
Student > Bachelor | 4 | 7% |
Student > Master | 4 | 7% |
Lecturer | 3 | 6% |
Other | 10 | 19% |
Unknown | 13 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 9 | 17% |
Medicine and Dentistry | 9 | 17% |
Neuroscience | 5 | 9% |
Agricultural and Biological Sciences | 5 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 7% |
Other | 7 | 13% |
Unknown | 15 | 28% |