ijms-logo

Journal Browser

Journal Browser

Special Issue "Protein Kinases and Their Inhibitors in CNS Diseases"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 31 July 2021.

Special Issue Editor

Prof. Dr. Ana Martínez
E-Mail Website
Guest Editor
Centro de Investigaciones Biologicas (CIB-CSIC), Ramiro de Maetzu 9, Madrid, Spain
Interests: drug design; medicinal chemistry; neurodegenerative diseases; pharmacology
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Protein kinases have emerged in the last years as good drugable targets for several diseases. More than 50 inhibitors have been approved by the regulatory agencies in the last  years mainly as anti-cancer drugs. Recently some others small molecules that inhibit different kinases starting to reach clinical practice for other chronic diseases such as inflammatory diseases. Neurodegenerative pathologies and different CNS disorders represents a great challenge for researchers as their pathomolecular mechanisms are not clearly established and their therapies are far from being effective. Protein kinases inhibitors gain stage as promising agents for neurological disorders. Some important challenges may be obtained as brain penetrant compounds, high selectivity sometimes through allosteric modulation, new and old kinases discovered in CNS system, etc....This special issue will try to collect recent advances in this field.

Prof. Dr. Ana Martínez
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com 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 papers will be 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Keywords

  • protein kinase inhibitors
  • CNS
  • ALS
  • Alzheimer
  • Parkinson
  • BBB

Published Papers (2 papers)

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

Research

Jump to: Review

Open AccessArticle
Neuroprotective Effect of Kinase Inhibition in Ischemic Factor Modeling In Vitro
Int. J. Mol. Sci. 2021, 22(4), 1885; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041885 - 14 Feb 2021
Viewed by 324
Abstract
The contribution of many neuronal kinases to the adaptation of nerve cells to ischemic damage and their effect on functional neural network activity has not yet been studied. The aim of this work is to study the role of the four kinases belonging [...] Read more.
The contribution of many neuronal kinases to the adaptation of nerve cells to ischemic damage and their effect on functional neural network activity has not yet been studied. The aim of this work is to study the role of the four kinases belonging to different metabolic cascades (SRC, Ikkb, eEF2K, and FLT4) in the adaptive potential of the neuron-glial network for modeling the key factors of ischemic damage. We carried out a comprehensive study on the effects of kinases blockade on the viability and network functional calcium activity of nerve cells under ischemic factor modeling in vitro. Ischemic factor modelling was performed on day 14 of culturing primary hippocampal cells obtained from mouse embryos (E18). The most significant neuroprotective effect was shown in the blockade of FLT4 kinase in the simulation of hypoxia. The studies performed revealed the role of FLT4 in the development of functional dysfunction in cerebrovascular accidents and created new opportunities for the study of this enzyme and its blockers in the formation of new therapeutic strategies. Full article
(This article belongs to the Special Issue Protein Kinases and Their Inhibitors in CNS Diseases)
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
c-Jun N-Terminal Kinase Inhibitors as Potential Leads for New Therapeutics for Alzheimer’s Diseases
Int. J. Mol. Sci. 2020, 21(24), 9677; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249677 - 18 Dec 2020
Cited by 2 | Viewed by 634
Abstract
Alzheimer’s Disease (AD) is becoming more prevalent as the population lives longer. For individuals over 60 years of age, the prevalence of AD is estimated at 40.19% across the world. Regarding the cognitive decline caused by the disease, mitogen-activated protein kinases (MAPK) pathways [...] Read more.
Alzheimer’s Disease (AD) is becoming more prevalent as the population lives longer. For individuals over 60 years of age, the prevalence of AD is estimated at 40.19% across the world. Regarding the cognitive decline caused by the disease, mitogen-activated protein kinases (MAPK) pathways such as the c-Jun N-terminal kinase (JNK) pathway are involved in the progressive loss of neurons and synapses, brain atrophy, and augmentation of the brain ventricles, being activated by synaptic dysfunction, oxidative stress, and excitotoxicity. Nowadays, AD symptoms are manageable, but the disease itself remains incurable, thus the inhibition of JNK3 has been explored as a possible therapeutic target, considering that JNK is best known for its involvement in propagating pro-apoptotic signals. This review aims to present biological aspects of JNK, focusing on JNK3 and how it relates to AD. It was also explored the recent development of inhibitors that could be used in AD treatment since several drugs/compounds in phase III clinical trials failed. General aspects of the MAPK family, therapeutic targets, and experimental treatment in models are described and discussed throughout this review. Full article
(This article belongs to the Special Issue Protein Kinases and Their Inhibitors in CNS Diseases)
Show Figures

Figure 1

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

1.Title: CK1-derived peptides as novel tools inhibiting the interactions between CK1 and APP695 to modulate the pathogenic metabolism of APP

Authors: Aileen Roth, Katja Mayer, Julian Beyrle, Irina König, Fabian Gärtner, Christoph Michalski, Uwe Knippschild and Joachim Bischof

 

Abstract: AD is a progressive neurodegenerative disorder, which is characterized by irreversible changes of specific neurons in the brain, leading to cognitive impairment followed by a mental and functional decline. Generally, AD is responsible for more than 80% of dementia cases in elderly people worldwide. Published data demonstrated a possible role for CK1 in the pathogenesis of AD by influencing the metabolism of tau and APP, which finally leads to formation of neurofibrillary tangles (NFTs) and accumulation of Aβ plaques followed by neuronal cell death. Therefore, CK1 can be seen as a therapeutic target in AD. An innovative strategy in treating AD could consequently be based on peptide inhibitors, which specifically modulate the interaction between CK1 and APP without impairing CK1 kinase activity in general. In this study, CK1-derived peptides manipulating the interaction between CK1δ/ε and APP695 were first identified by interaction analysis. Subsequently, dose-dependent effects on CK1-mediated phosphorylation of APP695 was detected for selected CK1-derived peptides in vitro. Most of these peptides also successfully passed the cell membrane in cell entry analysis and were finally tested for their effects on cellular APP metabolism. In summary, the results obtained in this study provide new insights to the interactions of CK1 with APP695 and identified CK1-derived peptides as promising approach for the development of novel pharmacological tools for the treatment of AD.

Back to TopTop