TY - JOUR
T1 - Therapeutic strategy for parkinson’s disease
T2 - Targeting zinc-binding protein in astrocytes
AU - Miyazaki, Ikuko
AU - Asanuma, Masato
N1 - Publisher Copyright:
© 2021 by The Japanese Pharmacological Society
PY - 2021
Y1 - 2021
N2 - Parkinson’s disease (PD) is a progressive neurodegenerative disease with motor symptoms, such as tremor, akinesia/bradykinesia, rigidity and postural instability due to a loss of nigrostriatal dopaminergic neurons; PD patients also exhibit non-motor symptoms, such as hyposmia, orthostatic hypotension and constipation, which precede motor symptoms. Pathologically, Lewy bodies and neurites, which contains α-synuclein, are observed in the central and peripheral nervous system. To date, it is hypothesized that PD pathology appears first in the olfactory bulb and the enteric nervous system, and propagates progressively through the substantia nigra to finally reach the cerebral cortex. Major medications at present are nosotropic treatments to improve motor dysfunction in PD. Therefore, development of disease-modifying drug is required to slow or prevent PD progression. Astrocytes are known to play an important role in the maintenance of the neuronal environment and exert neuroprotective effects by production of antioxidants and neurotrophic factors and clearing toxic molecules. In the previous study, we demonstrated that astrocytes produced antioxidative molecules metallothionein (MT)-1/2 in response to oxidative stress and protected dopaminergic neurons against oxidative stress. MTs are cysteine-rich proteins possessing antioxidative properties. MTs bind to metals such as zinc (Zn) and copper (Cu) and function in metal homeostasis and detoxification; MTs regulate Zn-mediated transcriptional activation of various genes. Recently, it is reported that MTs prevent Cu-induced aggregation of α-synuclein. In this article, we review a new therapeutic strategy of neuroprotection in PD by targeting MTs in astrocytes.
AB - Parkinson’s disease (PD) is a progressive neurodegenerative disease with motor symptoms, such as tremor, akinesia/bradykinesia, rigidity and postural instability due to a loss of nigrostriatal dopaminergic neurons; PD patients also exhibit non-motor symptoms, such as hyposmia, orthostatic hypotension and constipation, which precede motor symptoms. Pathologically, Lewy bodies and neurites, which contains α-synuclein, are observed in the central and peripheral nervous system. To date, it is hypothesized that PD pathology appears first in the olfactory bulb and the enteric nervous system, and propagates progressively through the substantia nigra to finally reach the cerebral cortex. Major medications at present are nosotropic treatments to improve motor dysfunction in PD. Therefore, development of disease-modifying drug is required to slow or prevent PD progression. Astrocytes are known to play an important role in the maintenance of the neuronal environment and exert neuroprotective effects by production of antioxidants and neurotrophic factors and clearing toxic molecules. In the previous study, we demonstrated that astrocytes produced antioxidative molecules metallothionein (MT)-1/2 in response to oxidative stress and protected dopaminergic neurons against oxidative stress. MTs are cysteine-rich proteins possessing antioxidative properties. MTs bind to metals such as zinc (Zn) and copper (Cu) and function in metal homeostasis and detoxification; MTs regulate Zn-mediated transcriptional activation of various genes. Recently, it is reported that MTs prevent Cu-induced aggregation of α-synuclein. In this article, we review a new therapeutic strategy of neuroprotection in PD by targeting MTs in astrocytes.
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U2 - 10.1254/fpj.20082
DO - 10.1254/fpj.20082
M3 - Article
C2 - 33642534
AN - SCOPUS:85102226653
VL - 156
SP - 76
EP - 80
JO - Folia Pharmacologica Japonica
JF - Folia Pharmacologica Japonica
SN - 0015-5691
IS - 2
ER -