Title:Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease
Volume: 23
Issue: 7
Author(s): Ikuko Miyazaki and Masato Asanuma
Affiliation:
Keywords:
5-HT1A receptor, S100β, astrocyte, Parkinson’s disease, neuroprotection, dopaminergic neuron.
Abstract: Astrocytes are the most abundant neuron-supporting glial cells in the central
nervous system. The neuroprotective role of astrocytes has been demonstrated in various
neurological disorders such as amyotrophic lateral sclerosis, spinal cord injury, stroke and
Parkinson’s disease (PD). Astrocyte dysfunction or loss-of-astrocytes increases the susceptibility
of neurons to cell death, while astrocyte transplantation in animal studies has therapeutic
advantage. We reported recently that stimulation of serotonin 1A (5-HT1A) receptors on
astrocytes promoted astrocyte proliferation and upregulated antioxidative molecules to act as a neuroprotectant
in parkinsonian mice. PD is a progressive neurodegenerative disease with motor symptoms such as
tremor, bradykinesia, rigidity and postural instability, that are based on selective loss of nigrostriatal dopaminergic
neurons, and with non-motor symptoms such as orthostatic hypotension and constipation based on
peripheral neurodegeneration. Although dopaminergic therapy for managing the motor disability associated
with PD is being assessed at present, the main challenge remains the development of neuroprotective or disease-
modifying treatments. Therefore, it is desirable to find treatments that can reduce the progression of dopaminergic
cell death. In this article, we summarize first the neuroprotective properties of astrocytes targeting
certain molecules related to PD. Next, we review neuroprotective effects induced by stimulation of 5-HT1A
receptors on astrocytes. The review discusses new promising therapeutic strategies based on neuroprotection
against oxidative stress and prevention of dopaminergic neurodegeneration.
