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Optimizing Mechanistic Rationale for Parkinson’s Disease Treatment

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: 1 September 2024 | Viewed by 830

Special Issue Editor


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Guest Editor
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Interests: hydroxylase; dopamine; substantia nigra; striatum; nigrostriatal; glutamate; acetylcholine; gamma-aminobutyric acid (GABA); locomotor; aging; Parkinson’s disease; animal models

Special Issue Information

Dear Colleagues,

Viable therapeutic approaches to treat Parkinson’s disease (PD) symptoms are limited. A major reason for this is that a sound mechanistic rationale is lacking. Major loss of tyrosine hydroxylase and nigrostriatal neurons occurs in PD. The loss of TH may be circumvented for some time by L-DOPA, the product of TH. However, this approach is not disease-modifying, the duration of L-DOPA application is limited in time, and side effects from the extended use of L-DOPA are very common. Other therapies, like GDNF, have produced ambiguous outcomes. Moreover, some studies have revealed that targeting striatal dopamine signaling does not represent an ideal approach given the major loss of axon terminals at disease diagnosis. This Special Issue is a call for papers that provide evidence for new mechanistic angles of therapeutic approaches to treat motor, and related cognitive, impairment in Parkinson’s disease. This includes targeting dopamine signaling in the substantia nigra, non-dopaminergic mechanisms, and evidence that the restoration of major loss of neuron terminals or dopamine signaling in striatum is possible. Also of keen interest are papers addressing the characteristics of animal models that best emulate human PD in terms of nigrostriatal neuron loss, pathology, and timing of motor decline. With the goal to translate mechanistic insights from animal models to the human patient, this collection of studies is expected to reveal viable new angles of helping patients maintain mobility against disease progression.

Prof. Dr. Michael Salvatore
Guest Editor

Manuscript Submission Information

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Keywords

  • substantia nigra
  • tyrosine hydroxylase
  • growth factors
  • neuroprotection
  • repurposed drugs
  • lifestyle interventions
  • dopamine
  • models of Parkinson’s disease
 

Published Papers (1 paper)

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Research

15 pages, 4003 KiB  
Article
Exploring the Regulation of Cytochrome P450 in SH-SY5Y Cells: Implications for the Onset of Neurodegenerative Diseases
by Alice Pifferi, Elda Chiaino, Jesus Fernandez-Abascal, Aoife C. Bannon, Gavin P. Davey, Maria Frosini and Massimo Valoti
Int. J. Mol. Sci. 2024, 25(13), 7439; https://doi.org/10.3390/ijms25137439 - 6 Jul 2024
Viewed by 548
Abstract
Human individual differences in brain cytochrome P450 (CYP) metabolism, including induction, inhibition, and genetic variation, may influence brain sensitivity to neurotoxins and thus participate in the onset of neurodegenerative diseases. The aim of this study was to explore the modulation of CYPs in [...] Read more.
Human individual differences in brain cytochrome P450 (CYP) metabolism, including induction, inhibition, and genetic variation, may influence brain sensitivity to neurotoxins and thus participate in the onset of neurodegenerative diseases. The aim of this study was to explore the modulation of CYPs in neuronal cells. The experimental approach was focused on differentiating human neuroblastoma SH-SY5Y cells into a phenotype resembling mature dopamine neurons and investigating the effects of specific CYP isoform induction. The results demonstrated that the differentiation protocols using retinoic acid followed by phorbol esters or brain-derived neurotrophic factor successfully generated SH-SY5Y cells with morphological neuronal characteristics and increased neuronal markers (NeuN, synaptophysin, β-tubulin III, and MAO-B). qRT-PCR and Western blot analysis showed that expression of the CYP 1A1, 3A4, 2D6, and 2E1 isoforms was detectable in undifferentiated cells, with subsequent increases in CYP 2E1, 2D6, and 1A1 following differentiation. Further increases in the 1A1, 2D6, and 2E1 isoforms following β-naphthoflavone treatment and 1A1 and 2D6 isoforms following ethanol treatment were evident. These results demonstrate that CYP isoforms can be modulated in SH-SY5Y cells and suggest their potential as an experimental model to investigate the role of CYPs in neuronal processes involved in the development of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Optimizing Mechanistic Rationale for Parkinson’s Disease Treatment)
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