PMID- 28284907
OWN - NLM
STAT- MEDLINE
DCOM- 20180321
LR  - 20190613
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 60
DP  - 2017 May
TI  - Minocycline protects, rescues and prevents knockdown transgenic parkin Drosophila 
      against paraquat/iron toxicity: Implications for autosomic recessive juvenile 
      parkinsonism.
PG  - 42-53
LID - S0161-813X(17)30036-0 [pii]
LID - 10.1016/j.neuro.2017.03.002 [doi]
AB  - Autosomal recessive Juvenile Parkinsonism (AR-JP) is a chronic, progressive 
      neurodegenerative disorder caused by mutation in the PARKIN gene, and invariably 
      associated with dopaminergic (DAergic) neuronal loss and brain iron accumulation. 
      Since current medical therapy is symptomatic and lacks significant 
      disease-modifying effects, other treatment approaches are urgently needed it. In 
      the present work, we investigate the role of minocycline (MC) in paraquat 
      (PQ)/iron-induced neurotoxicity in the Drosophila TH>parkin-RNAi/+ (w[*]; 
      UAS-parkin-RNAi; TH-GAL4) fly and have shown the following: (i) MC increased life 
      span and restored the locomotor activity of knockdown (KD) transgenic parkin 
      flies in comparison with the control (vehicle) group; (ii) MC at low (0.1 and 
      0.3mM) and middle (0.5mM) concentrations protected, rescued and prevented KD 
      parkin Drosophila against PQ toxicity. However, MC at high (1mM) concentration 
      aggravated the toxic effect of PQ; (iii) MC protected and rescued DAergic neurons 
      against the PQ toxic effect according to tyrosine hydroxylase 
      (TH)>green-fluorescent protein (GFP) reporter protein microscopy and anti-TH 
      Western blotting analysis; (iv) MC protected DAergic neurons against PQ/iron 
      toxicity; (v) MC significantly abridged lipid peroxidation (LPO) in the 
      protection, rescue and prevention treatment in TH>parkin-RNAi/+ flies against PQ 
      or iron alone or combined (PQ/iron)-induced neuronal oxidative stress (OS). Our 
      results suggest that MC exerts neuroprotection against PQ/iron-induced OS in 
      DAergic neurons most probably by the scavenging activity of reactive oxygen 
      species (ROS), and by chelating iron. Therefore, MC might be a potential 
      therapeutic drug to delay, revert, or prevent AR-JP.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Ortega-Arellano, Hector Flavio
AU  - Ortega-Arellano HF
AD  - Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, 
      University of Antioquia (UdeA), Calle 70 No. 52-21, and Calle 62 # 52-59, 
      Building 1, Room 412, SIU, Medellin, Colombia.
FAU - Jimenez-Del-Rio, Marlene
AU  - Jimenez-Del-Rio M
AD  - Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, 
      University of Antioquia (UdeA), Calle 70 No. 52-21, and Calle 62 # 52-59, 
      Building 1, Room 412, SIU, Medellin, Colombia. Electronic address: 
      marlene.jimenez@udea.edu.co.
FAU - Velez-Pardo, Carlos
AU  - Velez-Pardo C
AD  - Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, 
      University of Antioquia (UdeA), Calle 70 No. 52-21, and Calle 62 # 52-59, 
      Building 1, Room 412, SIU, Medellin, Colombia. Electronic address: 
      calberto.velez@udea.edu.co.
LA  - eng
PT  - Journal Article
DEP - 20170308
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Drosophila Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - E1UOL152H7 (Iron)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 6.3.2.- (park protein, Drosophila)
RN  - FYY3R43WGO (Minocycline)
RN  - PLG39H7695 (Paraquat)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Brain/*drug effects/metabolism
MH  - Dopaminergic Neurons/*drug effects/metabolism
MH  - Drosophila Proteins/*metabolism
MH  - Drosophila melanogaster
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Iron/*toxicity
MH  - Lipid Peroxidation/drug effects
MH  - Male
MH  - Minocycline/*administration & dosage
MH  - Motor Activity/drug effects
MH  - Neuroprotective Agents/*administration & dosage
MH  - Oxidative Stress/drug effects
MH  - Paraquat/*toxicity
MH  - Parkinsonian Disorders/drug therapy/*metabolism
MH  - Survival Analysis
MH  - Ubiquitin-Protein Ligases/*metabolism
OTO - NOTNLM
OT  - Iron
OT  - Lipid peroxidation
OT  - Minocyclin
OT  - Oxidative stress
OT  - Paraquat
OT  - Parkin
OT  - Parkinson's disease
EDAT- 2017/03/13 06:00
MHDA- 2018/03/22 06:00
CRDT- 2017/03/13 06:00
PHST- 2016/12/09 00:00 [received]
PHST- 2017/02/03 00:00 [revised]
PHST- 2017/03/06 00:00 [accepted]
PHST- 2017/03/13 06:00 [pubmed]
PHST- 2018/03/22 06:00 [medline]
PHST- 2017/03/13 06:00 [entrez]
AID - S0161-813X(17)30036-0 [pii]
AID - 10.1016/j.neuro.2017.03.002 [doi]
PST - ppublish
SO  - Neurotoxicology. 2017 May;60:42-53. doi: 10.1016/j.neuro.2017.03.002. Epub 2017 
      Mar 8.