In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 7 ( 2022-7-28), p. e0272085-
Abstract:
Parkinson’s disease (PD) is a neurodegenerative disease characterized by inclusions of aggregated α-synuclein (α-Syn). Oxidative stress plays a critical role in nigrostriatal degeneration and is responsible for α-Syn aggregation in PD. Vitamin C or ascorbic acid acts as an effective antioxidant to prevent free radical damage. However, vitamin C is easily oxidized and often loses its physiological activity, limiting its therapeutic potential. The objective of this study was to evaluate whether NXP031, a new compound we developed consisting of Aptamin C and Vitamin C, is neuroprotective against α-synucleinopathy. To model α-Syn induced PD, we stereotactically injected AAV particles overexpressing human α-Syn into the substantia nigra (SN) of mice. One week after AAV injection, NXP031 was administered via oral gavage every day for eight weeks. We found that oral administration of NXP031 ameliorated motor deficits measured by the rotarod test and prevented the loss of nigral dopaminergic neurons caused by WT-α-Syn overexpression in the SN. Also, NXP031 blocked the propagation of aggregated α-Syn into the hippocampus by alleviating oxidative stress. These results indicate that NXP031 can be a potential therapeutic for PD.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0272085
DOI:
10.1371/journal.pone.0272085.g001
DOI:
10.1371/journal.pone.0272085.g002
DOI:
10.1371/journal.pone.0272085.g003
DOI:
10.1371/journal.pone.0272085.g004
DOI:
10.1371/journal.pone.0272085.g005
DOI:
10.1371/journal.pone.0272085.s001
DOI:
10.1371/journal.pone.0272085.s002
DOI:
10.1371/journal.pone.0272085.s003
DOI:
10.1371/journal.pone.0272085.s004
DOI:
10.1371/journal.pone.0272085.r001
DOI:
10.1371/journal.pone.0272085.r002
DOI:
10.1371/journal.pone.0272085.r003
DOI:
10.1371/journal.pone.0272085.r004
DOI:
10.1371/journal.pone.0272085.r005
DOI:
10.1371/journal.pone.0272085.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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