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SMER28 binding to V...
SMER28 binding to VCP/p97 enhances both autophagic and proteasomal neurotoxic protein clearance
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Wrobel, L. (författare)
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- Hill, Sandra Malmgren, 1987 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Rubinsztein, D. C. (författare)
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(creator_code:org_t)
- 2022-08-28
- 2023
- Engelska.
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8627 .- 1554-8635. ; 19:4, s. 1348-1350
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The ability to maintain a functional proteome by clearing damaged or misfolded proteins is critical for cell survival, and aggregate-prone proteins accumulate in many neurodegenerative diseases, such as Huntington, Alzheimer, and Parkinson diseases. The removal of such proteins is mainly mediated by the ubiquitin–proteasome system and autophagy, and the activity of these systems declines in disease or with age. We recently found that targeting VCP/p97 with compounds like SMER28 enhances macroautophagy/autophagy flux mediated by the increased activity of the PtdIns3K complex I. Additionally, we found that SMER28 binding to VCP stimulates aggregate-prone protein clearance via the ubiquitin–proteasome system. This concurrent action of SMER28 on both degradation pathways resulted in the selective decrease in disease-causing proteins but not their wild-type counterparts. These results reveal a promising mode of VCP activation to counteract the toxicity caused by aggregate-prone proteins. © 2022 Informa UK Limited, trading as Taylor & Francis Group.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Aggregate-prone proteins
- autophagy activation
- PI3P
- SMER28
- ubiquitin–proteasome system
- VCP/p97
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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