POL Scientific / JBM / Volume 3 / Issue 3 / DOI: 10.14440/jbm.2016.124
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Protocol for evaluation of neurotrophic strategies in Parkinson

Shane V. Hegarty1 Aideen M. Sullivan1 Gerard W. O’Keeffe1,2
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1 Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland
2 The Irish Centre for Fetal and Neonatal Translational Research (INFANT), Cork University Maternity Hospital, Cork, Ireland
Published: 25 July 2016
© 2016 by the author. Licensee POL Scientific, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Parkinson’s disease (PD) is a neurodegenerative disease that is characterised by motor and non-motor symptoms which result from the progressive degeneration of nigrostriatal ventral midbrain (VM) dopaminergic (DA) neurons, as well as peripheral sympathetic neurons. PD is incurable, with current therapeutic strategies providing symptomatic relief. Neurotrophic factor (NTF) therapy has the potential to protect degenerating neurons in PD. However, there has been limited success in PD clinical trials due to neurotrophic strategies that are invasive, inefficient in delivering sustained neurotrophic support, do not protect all degenerating neurons and may have a compromised mechanism of action in the PD brain. Therefore, while neurotrophic therapy remains a promising disease-modifying approach for PD, it is important to identify novel neurotrophic strategies that can protect all neurons affected by PD. To address this need, we report an integrated approach for pre-clinical evaluation of potential neurotrophic strategies, e.g., pharmacological agents (e.g., drugs/small molecules), signalling proteins (e.g., morphogens) and/or genetic (gene/mRNA) modifications, in cellular models of the neuronal populations that are affected by PD. Herein, we describe, in detail, an in vitro protocol that allows a step-wise evaluation of the efficacy, and mechanism(s) of action, of novel neurotrophic strategies in VM DA neurons and sympathetic neurons, following an initial evaluation in a human cell line model of these cells, SH-SY5Y cells. The protocol uses the induction of neurite growth as the primary measure of neurotrophic action. Indeed, the neuro-protection/-restoration of PD-affected axons is widely thought to be an appropriate target for effective therapeutic intervention in PD.

Keywords
neurite growth analysis
dopaminergic neuron
Parkinson
neurotrophic therapy
sympathetic neuron
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Journal of Biological Methods, Electronic ISSN: 2326-9901 Print ISSN: TBA, Published by POL Scientific