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Cited by 28Alzheimer's disease research and treatmentsProtein Kinase Regulation and GTPase SignalingNeuroinflammation and Neurodegeneration Mechanisms

Inhibition of RhoA GTPase and the subsequent activation of PTP1B protects cultured hippocampal neurons against amyloid β toxicity

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Chacon, Pedro J, Garcia-Mejias, Rosa, Rodriguez-Tebar, Alfredo·2011·Molecular Neurodegeneration
DOI 10.1186/1750-1326-6-14PMC PMC3038970
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Abstract

Background: Amyloid beta (Aβ) is the main agent responsible for the advent and progression of Alzheimer's disease. This peptide can at least partially antagonize nerve growth factor (NGF) signalling in neurons, which may be responsible for some of the effects produced by Aβ. Accordingly, better understanding the NGF signalling pathway may provide clues as to how to protect neurons from the toxic effects of Aβ. Results: We show here that Aβ activates the RhoA GTPase by binding to p75 NTR, thereby preventing the NGF-induced activation of protein tyrosine phosphatase 1B (PTP1B) that is required for neuron survival. We also show that the inactivation of RhoA GTPase and the activation of PTP1B protect cultured hippocampal neurons against the noxious effects of Aβ. Indeed, either pharmacological inhibition of RhoA with C3 ADP ribosyl transferase or the transfection of cultured neurons with a dominant negative form of RhoA protects cultured hippocampal neurons from the effects of Aβ. In addition, over-expression of PTP1B also prevents the deleterious effects of Aβ on cultured hippocampal neurons. Conclusion: Our findings indicate that potentiating the activity of NGF at the level of RhoA inactivation and PTP1B activation may represent a new means to combat the noxious effects of Aβ in Alzheimer's disease.

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  • Aβ activates RhoA by binding to p75NTR, and inhibition of this receptor or RhoA directly prevents the deleterious effects of Aβ in hippocampal neurons.

    “Aβ activates RhoA by binding to the p75 neurotrophin receptor (p75NTR), and inhibition of this receptor or RhoA directly prevents the deleterious effects of Aβ in hippocampal neurons [186,196].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [186]

    The Discussion states that Aβ activates RhoA by binding to p75NTR. The Results show that inhibiting p75NTR signalling or RhoA counteracts Aβ’s effects in cultured hippocampal neurons, but TAT-pep5 rescued only around half the neurons from Aβ-induced death. Thus, saying the interventions prevent the deleterious effects without qualification overstates the survival result (page numbers unavailable in our copy). (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Chacon, P. J., Garcia-Mejias, R., & Rodriguez-Tebar, A.
Affiliations
Centro Andaluz de Biología Molecular y Medicina Regenerativa (ES)
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2011-02-04
Volume
6
Issue
1
Pages
14-14
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/1750-1326-6-14
PMC
PMC3038970
OpenAlex
W2142483960
Cited by
28
References
4
Citations by year
2025: 2 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 1 · 2017: 1 · 2015: 5 · 2014: 5 · 2013: 2 · 2012: 4
FWCI
2.27
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Deposito de Investigacion Universidad de Sevilla (University of Seville) (publishedVersion, cc-by-nc-nd)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders
Instituto de Salud Carlos III
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid-beta, RhoA GTPase, PTP1B, p75 neurotrophin receptor, hippocampal neurons, neuronal survival, Alzheimer's disease, dominant-negative RhoA, neuroprotection

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