title: Neuroprotective effects of protocatechuic aldehyde against neurotoxin-induced cellular and animal models of Parkinson's disease.
abstract: Protocatechuic aldehyde (PAL) has been reported to bind to DJ-1, a key protein involved in Parkinson's disease (PD), and exerts potential neuroprotective effects via DJ-1 in SH-SY5Y cells. In this study, we investigated the neuroprotective pharmacological effects of PAL against neurotoxin-induced cell and animal models of PD. In cellular models of PD, PAL markedly increased cell viability rates, mitochondrial oxidation-reduction activity and mitochondrial membrane potential, and reduced intracellular ROS levels to prevent neurotoxicity in PC12 cells. In animal models of PD, PAL reduced the apomorphine injection, caused turning in 6-OHDA treated rats, and increased the motor coordination and stride decreases in MPTP treated mice. Meanwhile, in an MPTP mouse model, PAL prevented a decrease of the contents of dopamine (DA) and its metabolites in the striatum and TH-positive dopaminergic neuron loss in the substantia nigra (SN). In addition, PAL increased the protein expression of DJ-1 and reduced the level of α-synuclein in the SN of MPTP lesioned mice. PAL also increased the spine density in hippocampal CA1 neurons. The current study demonstrates that PAL can efficiently protect dopaminergic neurons against neurotoxin injury in vitro and in vivo, and that the potential mechanisms may be related to its effects in increasing DJ-1, decreasing α-synuclein and its growth-promoting effect on spine density.
authors.affiliation: National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, P. R. China ; Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Shenyu
authors.initials: S
authors.lastname: Zhai
authors.forename: Ming-Sheng
authors.initials: MS
authors.lastname: An
authors.forename: Yue-Hua
authors.initials: YH
authors.lastname: Wang
authors.forename: Ying-Fan
authors.initials: YF
authors.lastname: Yang
authors.forename: Hui-Qi
authors.initials: HQ
authors.lastname: Ge
authors.forename: Jin-Hao
authors.initials: JH
authors.lastname: Liu
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Pu
mesh_terms: D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000009:adverse effects* / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D001547:Benzaldehydes; D002396:Catechols; D018696:Neuroprotective Agents; D009498:Neurotoxins; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; C005581:protocatechualdehyde; D004298:Dopamine