Neuroprotective effects of 2,4-dinitrophenol in an acute model of Parkinson's disease.
Neurons depend on mitochondria for homeostasis and survival, and thus, mitochondrial dysfunction has been implicated in neurodegenerative diseases, including Parkinson's disease (PD). Increasing evidence indicates the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), protects neurons against neurodegeneration and enhances neural plasticity. Here, the authors evaluated the protective effects of intraperitoneally (i.p.) administered low dose DNP in an acute mouse model of PD. Mice were administered DNP (1 or 5mg/kg) for 12 consecutive days, and then on day 13, MPTP (20mg/kg, i.p.) was administered four times (with 2h intervals between injections) to induce PD. It was found that MPTP-induced motor dysfunction was ameliorated in the DNP-treated mice versus vehicle-treated controls. Additionally, DNP effectively attenuated dopaminergic neuronal loss observed in MPTP treated mice. Moreover, in primary cultured neurons, DNP at 10μM, but not at 100μM, prevented MPP+-induced cell death and mitochondrial membrane potential (MMP) reduction. In addition, DNP was observed to cause the nuclear translocation of Nrf2 in primary neurons. Taken together, these findings of the present study suggest that DNP protects dopaminergic neurons against neurodegeneration and maintains MMP integrity in PD by activating adaptive stress responses.
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
Yujeong
Y
Lee
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
Gwangbeom
G
Heo
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
Kyung Moon
KM
Lee
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
Ah Hyun
AH
Kim
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
Ki Wung
KW
Chung
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
Eunok
E
Im
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
Hae Young
HY
Chung
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: neuron@pusan.ac.kr.
Jaewon
J
Lee
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D019297:2,4-Dinitrophenol / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004140:Dinitrophenols / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects; D020267:MPTP Poisoning / Q000503:physiopathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects
D004140:Dinitrophenols; D018696:Neuroprotective Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019297:2,4-Dinitrophenol; D004298:Dopamine
1-Methyl-4-phenyl-1/2/3/6-tetrahydropyridine (MPTP); 2/4-Dinitrophenol (DNP); Mitochondrial dysfunction; Mitochondrial uncoupler; Parkinson’s disease