Cytotoxic Mechanisms of Ribosome-Inactivating Proteins and Related Immunotoxins

A special issue of Stresses (ISSN 2673-7140). This special issue belongs to the section "Animal and Human Stresses".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 2323

Special Issue Editor

E-Mail Website
Guest Editor
Department of Medical and Surgical Sciences-DIMEC, General Pathology Section, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
Interests: Xanthine oxidoreductase; oxidative stress; uric acid; nitric oxide; cytotoxicity; plant toxin; rRNA glycosylase; immunotoxin; targeted therapy; anti-tumour therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ribosome-inactivating proteins (RIPs) are toxic plant enzymes with rRNA N-glycosylase activity that can remove a specific adenine residue from 28S rRNA, thus causing the irreversible inhibition of protein synthesis and cell death. In addition, some authors have reported that RIPs are able to deadenylate several other substrates such as poly(A), mRNA, tRNA, and DNA, thus displaying polynucleotide:adenine glycosylase activity.

For many years, rRNA deadenylation was thought to be the only enzymatic activity of RIPs, and ribosome inactivation was considered the pivotal event in cell death triggering. Apoptotic changes in cells intoxicated with ricin or abrin were firstly described in 1987, and subsequently, apoptosis was commonly considered the typical mode of RIP-induced cell death. However, several lines of experimental evidence demonstrate that RIP intoxication can induce multiple cell death pathways, involving at least apoptosis, necroptosis and autophagy. Moreover, it is now evident that RIPs can induce apoptosis regardless of protein synthesis inhibition. Despite the progress made in the knowledge of the pathogenetic mechanisms of these molecules, many points still need to be clarified. Among these are the primary molecular events induced by RIP intoxication, the correlation between the cell differentiation degree and RIP sensitivity, the interconnection between different cell death pathways, and the timing of all these events.

RIPs have been used in many experimental strategies in medicine, in order to specifically destroy cells responsible for pathological conditions. These plant toxins have been tested as native molecules, in locoregional treatments, or as toxic components of immunotoxins for experimental therapy in several pathologies, ranging from cancer and pain control to autoimmune diseases and transplant rejection. The elucidation of the molecular details of cell intoxication by RIP is a fundamental requirement for building increasingly effective immunotoxins and predicting, in part, their possible side effects.

The aim of this Special Issue is to collect original articles, reviews and short communications that provide readers with a comprehensive and clear overview of the cell stress mechanisms and death pathways induced by RIPs.

Dr. Andrea Bolognesi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Stresses is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • plant toxins
  • lectins
  • ribosome-inactivating proteins (RIP)
  • rRNA N-glycosylases
  • polynucleotide:adenosine glycosidase
  • immunotoxins
  • immunotargeting
  • apoptosis
  • necroptosis
  • ribotoxic stress
  • oxidative stress
  • unfolded protein response
  • signal transduction

Published Papers (1 paper)

Order results
Result details
Select all
Export citation of selected articles as:


12 pages, 2140 KiB  
Plant Toxins as Potential Alternatives to Botulinum Toxin for Eye-Movement Disorder Therapy
by Massimo Bortolotti, Andrea Zanello, Lorenzo Serra, Francesco Biscotti, Letizia Polito and Andrea Bolognesi
Stresses 2023, 3(1), 270-281; - 1 Feb 2023
Cited by 2 | Viewed by 1605
The most successful alternative to traditional surgery for ocular muscle spasm treatment is the intramuscular injection of botulinum toxin (BTX), which allows the maintenance of the muscle dynamics and the absence of scars. However, the main BTX disadvantage is its nonpermanent effect. A [...] Read more.
The most successful alternative to traditional surgery for ocular muscle spasm treatment is the intramuscular injection of botulinum toxin (BTX), which allows the maintenance of the muscle dynamics and the absence of scars. However, the main BTX disadvantage is its nonpermanent effect. A possible way for overcoming this obstacle could be represented by the enzymatic surgery using plant toxins known as ribosome-inactivating proteins (RIPs). In this paper, two highly toxic RIPs, namely, ricin and stenodactylin, were considered in a preliminary study for their possible use in the treatment of strabismus and oculofacial dystonias, as alternatives to BTX. Both RIPs showed a strong cytotoxic effect against rhabdomyosarcoma cell lines and myotube differentiated cells, with stenodactylin being about 10-fold more toxic than ricin. Moreover, stenodactylin showed a much higher cytotoxicity on myoblasts than on rhabdomyosarcoma cells. In our experimental conditions, stenodactylin did not damage conjunctival cells. Despite the limitations due to in vitro experiments, our data show that the high cytotoxicity of stenodactylin allows the use of a very low dose and, consequently, of very low injection volumes. This can represent a great advantage in the case of in vivo locoregional treatment. Furthermore, it is possible to modulate the chemoablation of myocytes while destroying myoblasts, thus reducing regenerative phenomena. The risk of cytotoxicity to surrounding tissues would be strongly reduced by the low injected volume and the relative resistance of conjunctival cells. In conclusion, our data suggest that stenodactylin and ricin could represent potential candidates to substitute BTX in ocular dystonia therapy. Full article
Show Figures

Figure 1

Back to TopTop