PMID- 28571715
OWN - NLM
STAT- MEDLINE
DCOM- 20180417
LR  - 20180417
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 123
DP  - 2017 Sep 1
TI  - The novel multitarget iron chelating and propargylamine drug M30 affects APP 
      regulation and processing activities in Alzheimer's disease models.
PG  - 359-367
LID - S0028-3908(17)30251-4 [pii]
LID - 10.1016/j.neuropharm.2017.05.026 [doi]
AB  - In many of the neurodegenerative diseases, such as Alzheimer's disease (AD) and 
      AD-related disorders, as well as in the regular ageing process, excessive 
      generation of oxidative stress (OS) and accumulation of iron levels and 
      deposition have been observed in specific affected-brain regions and thus, 
      regarded as contributing factors to the pathogenesis of the diseases. In AD, iron 
      promotes amyloid beta (Abeta) neurotoxicity by producing free radical damage and OS in 
      brain areas affected by neurodegeneration, presumably by facilitating the 
      aggregation of Abeta. In addition, it was shown that iron modulates intracellular 
      levels of the holo amyloid precursor protein (APP) by iron-responsive elements 
      (IRE) RNA stem loops in the 5' untranslated region (5'UTR) of the APP transcript. 
      As a consequence of these observations, iron chelation is one of the major new 
      therapeutic strategies for the treatment of AD. This review describes the 
      benefits and importance of the multimodal brain permeable chimeric 
      iron-chelating/propargylamine drug M30, concerning its 
      neuroprotective/neurorestorative inter-related activities relevant of the 
      pathological features ascribed to AD, with a special focus on the effect of the 
      drug on APP regulation and processing.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Amit, Tamar
AU  - Amit T
AD  - Faculty of Medicine, Technion- Israel Institute of Technology, Haifa 31096, 
      Israel.
FAU - Bar-Am, Orit
AU  - Bar-Am O
AD  - Faculty of Medicine, Technion- Israel Institute of Technology, Haifa 31096, 
      Israel.
FAU - Mechlovich, Danit
AU  - Mechlovich D
AD  - Faculty of Medicine, Technion- Israel Institute of Technology, Haifa 31096, 
      Israel.
FAU - Kupershmidt, Lana
AU  - Kupershmidt L
AD  - Faculty of Medicine, Technion- Israel Institute of Technology, Haifa 31096, 
      Israel.
FAU - Youdim, Moussa B H
AU  - Youdim MBH
AD  - Faculty of Medicine, Technion- Israel Institute of Technology, Haifa 31096, 
      Israel.
FAU - Weinreb, Orly
AU  - Weinreb O
AD  - Faculty of Medicine, Technion- Israel Institute of Technology, Haifa 31096, 
      Israel. Electronic address: worly@technion.ac.il.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170529
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Hydroxyquinolines)
RN  - 0 (Iron Chelating Agents)
RN  - 0 (Neuroprotective Agents)
SB  - IM
MH  - Alzheimer Disease/*drug therapy/*metabolism
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Humans
MH  - Hydroxyquinolines/*pharmacology
MH  - Iron Chelating Agents/*pharmacology
MH  - Neuroprotective Agents/*pharmacology
OTO - NOTNLM
OT  - APP processing/regulation
OT  - Alzheimer's disease
OT  - Amyloid beta
OT  - Iron chelation
OT  - Propargyl moiety
EDAT- 2017/06/03 06:00
MHDA- 2018/04/18 06:00
CRDT- 2017/06/03 06:00
PHST- 2017/04/04 00:00 [received]
PHST- 2017/05/16 00:00 [revised]
PHST- 2017/05/26 00:00 [accepted]
PHST- 2017/06/03 06:00 [pubmed]
PHST- 2018/04/18 06:00 [medline]
PHST- 2017/06/03 06:00 [entrez]
AID - S0028-3908(17)30251-4 [pii]
AID - 10.1016/j.neuropharm.2017.05.026 [doi]
PST - ppublish
SO  - Neuropharmacology. 2017 Sep 1;123:359-367. doi: 10.1016/j.neuropharm.2017.05.026. 
      Epub 2017 May 29.