Abstract
The transcription factor Pax6 is a well-accepted neurogenic determinant during development, in adult neural progenitor cells and in acute brain injury models. In the adult brain Pax6 is expressed in selective populations of dopaminergic neurons, and thus may have a role to play in Parkinson’s disease (PD). This study looked at post-mortem tissue from patients with PD and in particular the substantia nigra which showed a reduced number of PAX6+ cells compared to age and sex matched control tissue. In an animal model of PD, there was an early transient increase in the number of SN Pax6+ cells at the time of cell loss through apoptosis. Finally we showed that an over-expression of Pax6 in SH-SY5Y cells treated with PD relevant neurotoxins, resulted in an increase in cell survival and a reduction in markers of apoptosis and oxidative stress. These results suggest that Pax6 may have a role to play in the loss of dopaminergic neurons in PD.
Keywords: PAX6, dopamine, neuroprotection, apoptosis, SH-SY5Y.
CNS & Neurological Disorders - Drug Targets
Title:PAX6 expression may be protective against dopaminergic cell loss in Parkinson’s disease
Volume: 15 Issue: 1
Author(s): Meghan G. Thomas, Caitlyn Welch, Leah Stone, Peter Allan, Roger A. Barker and Robert B. White
Affiliation:
Keywords: PAX6, dopamine, neuroprotection, apoptosis, SH-SY5Y.
Abstract: The transcription factor Pax6 is a well-accepted neurogenic determinant during development, in adult neural progenitor cells and in acute brain injury models. In the adult brain Pax6 is expressed in selective populations of dopaminergic neurons, and thus may have a role to play in Parkinson’s disease (PD). This study looked at post-mortem tissue from patients with PD and in particular the substantia nigra which showed a reduced number of PAX6+ cells compared to age and sex matched control tissue. In an animal model of PD, there was an early transient increase in the number of SN Pax6+ cells at the time of cell loss through apoptosis. Finally we showed that an over-expression of Pax6 in SH-SY5Y cells treated with PD relevant neurotoxins, resulted in an increase in cell survival and a reduction in markers of apoptosis and oxidative stress. These results suggest that Pax6 may have a role to play in the loss of dopaminergic neurons in PD.
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Thomas G. Meghan, Welch Caitlyn, Stone Leah, Allan Peter, Barker A. Roger and White B. Robert, PAX6 expression may be protective against dopaminergic cell loss in Parkinson’s disease, CNS & Neurological Disorders - Drug Targets 2016; 15 (1) . https://dx.doi.org/10.2174/1871527314666150821101757
DOI https://dx.doi.org/10.2174/1871527314666150821101757 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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