TY - JOUR
T1 - Therapeutic strategy of targeting astrocytes for neuroprotection in parkinson’s disease
AU - Miyazaki, Ikuko
AU - Asanuma, Masato
N1 - Funding Information:
This work was supported by Grants-in-Aid for Young Scientists (B) (grant number: 18700364 to I.M.), for Scientific Research (C) (grant number: 21591082 to M.A., 22590934, 25461279 and 16K09673 to I.M.) from Japan Society for the Promotion of Science, by Grant-in Aid for Scientific Research on Innovative Areas ?Brain Environment? from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (grant number: 24111533 to M.A.), by the Okayama Medical Foundation, Kawasaki Foundation for Medical Science & Medical Welfare (to I.M.).
Publisher Copyright:
© 2017 Bentham Science Publishers.
PY - 2017
Y1 - 2017
N2 - Parkinson’s disease (PD) is one of common neurodegenerative diseases, which shows motor symptoms including tremor, bradykinesia, rigidity and postural instability. It also involves non-motor symptoms such as cognitive impairment, mental manifestation, autonomic disorder and sensory disturbance. Although treatments to improve the motor disability in PD are being assessed at present, the main challenge remains that is the development of neuroprotective or disease-modifying treatments. Therefore, it is desirable to find approaches that can inhibit the progression of dopaminergic neurodegeneration. Astrocytes are known to play an important role in the maintenance of the neuronal environment and exert neuroprotective effects. Additionally, astrocyte dysfunction increases the susceptibility of neurons to cytotoxicity. We have demonstrated neuroprotective approaches in parkinsonian models in various studies targeting astrocytes. In this article, we summarize the neuroprotective function of astrocytes in the brain, involvement of astrocyte dysfunction in neurodegeneration, and experimental approaches to dopaminergic neuroprotection. We review findings reported in several papers including our own studies. We also address target molecules and pivotal pathways in astrocytes for dopaminergic neuroprotection. The review discusses new promising therapeutic strategies to prevent dopaminergic neurodegeneration in PD.
AB - Parkinson’s disease (PD) is one of common neurodegenerative diseases, which shows motor symptoms including tremor, bradykinesia, rigidity and postural instability. It also involves non-motor symptoms such as cognitive impairment, mental manifestation, autonomic disorder and sensory disturbance. Although treatments to improve the motor disability in PD are being assessed at present, the main challenge remains that is the development of neuroprotective or disease-modifying treatments. Therefore, it is desirable to find approaches that can inhibit the progression of dopaminergic neurodegeneration. Astrocytes are known to play an important role in the maintenance of the neuronal environment and exert neuroprotective effects. Additionally, astrocyte dysfunction increases the susceptibility of neurons to cytotoxicity. We have demonstrated neuroprotective approaches in parkinsonian models in various studies targeting astrocytes. In this article, we summarize the neuroprotective function of astrocytes in the brain, involvement of astrocyte dysfunction in neurodegeneration, and experimental approaches to dopaminergic neuroprotection. We review findings reported in several papers including our own studies. We also address target molecules and pivotal pathways in astrocytes for dopaminergic neuroprotection. The review discusses new promising therapeutic strategies to prevent dopaminergic neurodegeneration in PD.
KW - 5-hT1A receptor
KW - Antioxidative molecules
KW - Astrocyte
KW - Dopaminergic neuron
KW - Neuroprotection
KW - Nrf2
KW - Parkinson’s disease
KW - XCT
UR - http://www.scopus.com/inward/record.url?scp=85041640471&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041640471&partnerID=8YFLogxK
U2 - 10.2174/1381612823666170710163731
DO - 10.2174/1381612823666170710163731
M3 - Review article
C2 - 28699520
AN - SCOPUS:85041640471
SN - 1381-6128
VL - 23
SP - 4936
EP - 4947
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 33
ER -