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.
Title: Mitocondrial Disfunction in CIPN
Authors: A. Canta 1, E. Pozzi 1 and V.A. Carozzi 1,2
Affiliations: 1Department of Surgery and Translational Medicine, University of Milan-Bicocca, Via Cadore 48, 20900 Monza (MB), Italy; Phone: +39-02 6448 8122 Fax: +39-02 6448 8250
2Young Against Pain Group
Abstract: The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced painful peripheral neuropathies (CIPPN). This is due to a related disregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by a loss of mitochondrial membrane potential, increased generation of reactive oxygen species, a reduction in ATP level, calcium release and mitochondrial swelling. Cisplatin, forms adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons leading to a gradual energy failure. Moreover, changes in the expression in a number of genes including those of controlling mitochondrial functions were altered in patients with paclitaxel, vincristine and bortezomib-induced peripheral neuropathy.
Type of paper: Review
Title: L-dopa and Brain Serotonin System Dysfunction
Authors: Branden J. Stansley and Bryan K. Yamamoto
Affiliation: University of Toledo College of Medicine, Toledo, OH 43614, USA; E-Mail: Bryan.Yamamoto@utoledo.edu (B.K.Y.)
Abstract: L-dopa is used to treat the motor symptoms associated with Parkinson’s disease, a neurodegenerative disorder characterized by a loss of dopamine neurons. L-dopa is the precursor to dopamine and crosses the blood-brain barrier to elevate dopamine content. The review will show that dopamine produced from L-dopa is mediated in part by serotonin neurons. Evidence will be presented showing that increases in dopamine cause oxidative stress which damages serotonin neurons. Similarly, chronic L-dopa produces deficits in serotonin neurotransmission, including decreases in both serotonin cell bodies within the dorsal raphe and serotonin neurotransmitter concentrations in several forebrain regions. Since serotonin is involved in many important physiological processes including mood and cognition, L-dopa induced serotonin deficits may play a role in the side effect symptoms observed in Parkinson’s disease patients treated with L-dopa.
Type of paper: Review
Title: Current View in Platinum Drugs Mechanisms of Peripheral Neurotoxicity
Authors: Alessia Chiorazzi, Sara Semperboni and Paola Marmiroli
Affiliation: Department of Surgery and Translational Medicine, University of Milano-Bicocca, Monza (MB), Italy; E-Mail: email@example.com (A.C.)
Abstract: Peripheral neurotoxicity is the dose-limiting factor for the clinical use of platinum derivatives that are a class of anticancer drugs which includes cisplatin, carboplatin and oxaliplatin. In particular cisplatin and oxaliplatin induce a severe peripheral neurotoxicity while carboplatin is less neurotoxic.
The mechanisms proposed to explain neurotoxicity of these drugs are alteration of dorsal root ganglia, involvement of oxidative stress and mitochondrial dysfunction. Oxaliplatin also causes an acute and reversible painful neuropathy, supposed to be caused by a transient dysfunction of the voltage-gated sodium channels of peripheral nerves. Recent studies suggest that individual genetic variation may play a role in the pathogenesis of platinum drugs neurotoxicity.
Even though many mechanisms explaining neurotoxicity of these drugs have been proposed, the pathogenesis is far to be clearly defined.
In this review we will summarize the current knowledge and the most up-to-date hypothesis on the pathogenesis of this kind of peripheral neuropathy.
Type of paper: Review
Title: Taxane-Induced Peripheral Neuropathy
Authors: Roser Velasco 1,2 and Jordi Bruna 1,2
Affiliation: 1 Unit of Neuro-Oncology, Hospital Universitari Bellvitge-ICO L'Hospitalet, Spain; E-Mail: firstname.lastname@example.org (J.B.)
2 Group of Neuroplasticity and Regeneration, CIBERNED, Institute of Neuroscience and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barelona, Spain
Abstract: Taxane-derived agents are a type of chemotherapy drugs widely employed in cancer treatment. Among them, paclitaxel and docetaxel are most commonly administered, but newer formulations are being investigated. Taxane antineoplastic activity is mainly based on their ability to promote microtubule assembly, leading to mitotic arrest and apoptosis in cancer cells. Peripheral neurotoxicity is the major non-hematological adverse effect of taxane, often as painful neuropathy, experienced during the treatment and sometimes irreversibly. Unfortunately, taxane-induced neurotoxicity is an uncertainty prior the initiation of treatment. Present review tries to dissect current knowledge on real incidence, underlying pathophysiology, clinical features and predisposing factors related with taxane-induced neuropathy development.
Type of paper: Article
Title: Neurotoxic Effects of Platinum Compounds: Studies in vivo on Central Nervous System
Authors: G. Bernocchi, F.P. Fanizzi, S.A. De Pascali, V. Insolia, V.M. Piccolini and M.G. Bottone
Affiliations: 1 Dipartimento di Biologia e Biotecnologie "L. Spallanzani" Università di Pavia, via Ferrata 9, 27100, Pavia, Italy
2 Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.), Salento University, Lecce, Italy
Abstract: Platinum compounds are known to cause significant clinical neurotoxicity. Several studies highlight neurological complications especially in paediatric oncology patients with CNS and non-CNS malignancies.
To understand the toxicity mechanisms of platinum drugs at cellular and molecular levels in the immature brain, which is much more vulnerable to injury than the adult one, we compared the effects in vivo of the most used platinum compound, i.e., cisdichlorodiammineplatinum (cisplatin, cisPt), with that of a new platinum compound [Pt(O,O'-acac)(γ-acac)(DMS)] (PtAcacDMS). As models of developing brain areas we have chosen the hippocampus gyrus dentatus and cerebellum. Both areas show the events of the neurogenesis process, from proliferation to differentiation and formation of synaptic contacts, and therefore permit to compare the action of platinum compounds with different target, e.g., on DNA and non-DNA target. Here we focused the localization and identification of changes in the intracellular calcium within CNS architecture. At this purpose, we used two immunohistochemical markers of calcium homeostasis system, the calcium buffer protein Calbindin (CB) and Plasma Membrane Calcium ATPase (PMCA1).
From the comparison of the cisPt and PtAcacDMS effects it emerges how essential is the equilibrium and synergy between CB and PMCA1 to warrant the morphology and function of nervous tissue and limit neuroarchitecture damages, obviously depending by the peculiar and intrinsic properties of the developing CNS areas.
Type of paper: Review
Title: Toxicity of Bortezomib
Author: C. Meregalli
Affiliation: Department of Surgery and Translational Medicine, University of Milan Bicocca, Via Cadore 48, 20900 Monza (MB), Italy; Phone: +39 0264488122, Fax: +39 0264488250; E-Mail: email@example.com
Abstract: The boronic acid dipeptide Bortezomib is the first proteasome inhibitor drug to enter into clinical practice, able to induce tumor cell death by degradation of key proteins. It is employed as first-line treatment in relapsed or resistant multiple myeloma (MM) patients. However, bortezomib often induces a dose-limiting toxicity as painful sensory neuropathy, which has been reduced mainly by subcutaneous administration or dose modification. In this review we focus on the understanding of pathophysiological mechanisms of bortezomib-induced neuropathy to allow further studies in animal models and humans, including clinical and pharmacogenetic aspects, to optimize the treatment regimens.