A neuroprotective chemical, AJ29, prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson’s disease
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1
Konkuk University, Department of Applied Life Science, BK21plus Glocal Education program of Nutraceuticals Development, Republic of Korea
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2
Konkuk University, Department of Biotechnology, Republic of Korea
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3
Ajou University, Department of Molecular Science and Technology, Republic of Korea
Parkinson’s disease (PD) is characterized by the selective loss of nigrostriatal dopamine neurons associated with microglial activation. Therefore, inhibition of the inflammatory response elicited by activated microglia would be an effective strategy to alleviate PD process. In this study, we synthesized and investigated the molecular mechanisms of AJ29, a neuroprotective chemical derived from rimonabant, to protect lipopolysaccharide (LPS)-induced neuroinflammation in vitro and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in vivo. The results indicated that AJ29 significantly inhibited activated microglia released proinflammatory mediators such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), and proinflammatory cytokines. Mechanistic study revealed that AJ29 mitigated the LPS-induced nuclear factor kappaB (NF-kappaB) activation, inhibitor of kappaB alpha (IkappaB-alpha), and p38 phosphorylation in BV2 cells. Moreover, MPTP intoxication of mice resulted in glial activation, tyrosine hydroxylase (TH) depletion, and significant behavioral deficits. Prophylactic treatment with AJ29 decreased proinflammatory molecules via NF-kappaB and p38 mitogen-activated protein (MAP) kinase signaling, protected dopaminergic (DA) neurons and attenuated behavioral impairments. These results suggest that AJ29 is a promising neuroprotective agent for preventing and treating microglia-mediated neuroinflammatory conditions and may be useful for behavioral improvement in PD pathology.
Keywords:
Neuroprotection,
Parkinson’s disease,
in vivo,
in vitro,
behavioural deficit
Conference:
14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016.
Presentation Type:
Poster Presentation Session
Topic:
14th Meeting of the Asian-Pacific Society for Neurochemistry
Citation:
KIM
B,
PARK
J,
Ko
H,
Kim
I,
Yoon
S and
Choi
D
(2016). A neuroprotective chemical, AJ29, prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson’s disease.
Conference Abstract:
14th Meeting of the Asian-Pacific Society for Neurochemistry.
doi: 10.3389/conf.fncel.2016.36.00141
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Received:
04 Aug 2016;
Published Online:
11 Aug 2016.
*
Correspondence:
Dr. Byung-Wook KIM, Konkuk University, Department of Applied Life Science, BK21plus Glocal Education program of Nutraceuticals Development, Chungju-si, Chungcheongbuk-do, Republic of Korea, kb62@lycos.co.kr