PMID- 24262165
OWN - NLM
STAT- MEDLINE
DCOM- 20140711
LR  - 20131122
IS  - 1873-5126 (Electronic)
IS  - 1353-8020 (Linking)
VI  - 20 Suppl 1
DP  - 2014 Jan
TI  - Promises of novel multi-target neuroprotective and neurorestorative drugs for 
      Parkinson's disease.
PG  - S132-6
LID - S1353-8020(13)70032-4 [pii]
LID - 10.1016/S1353-8020(13)70032-4 [doi]
AB  - The cascade of neurotoxic events involved in neuronal degeneration suggests that 
      it is naive to think mono-target drugs can induce disease modification by slowing 
      the process of neurodegeneration in Parkinson's disease (PD). Employing the 
      pharmacophore of rasagiline (N-propargyl-1-R-aminoindan), we have developed a 
      series of novel multi-target neuroprotective drugs, including: (A) drugs 
      [ladostigil, TV-3326 (N-propargyl-3R-aminoindan-5yl)-ethyl methylcarbamate)] with 
      both cholinesterase-butyrylesterase (Ch-BuE) and brain-selective monamine 
      oxidase-AB (MAO-AB) inhibitory activities and (B) iron chelator-radical 
      scavenging drugs (M30) possessing brain-selective MAO-AB inhibitor activity and 
      the neuroprotective-neurorescue propargylamine moiety of rasagiline. This was 
      considered to be valid since brain MAO and iron increase in PD and aging, which 
      could lead to oxidative stress-dependent neurodegeneration. The multi-target iron 
      chelator, M30, has all the properties of ladostigil, but is not an 
      acetylcholinesterase (CHE) inhibitor. However, M30 has both neuroprotective and 
      neurorestorative activities for nigrostriatal dopamine neurons in post-lesion 
      MPTP, lactacystin and 6-hydroxydopamine animal models of PD. The neurorestorative 
      activity has been identified as being related to the ability of the drug to 
      activate hypoxia-inducible factor (HIF) by inhibiting prolyl-4-hydroxylase. M30 
      regulates cell cycle arrest and induces the neurotrophins brain-derived 
      neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), 
      erythropoietin (EPO), as well as glia-derived neurotrophic factor (GDNF). These 
      unique multiple actions of M30 make it potentially useful as a disease modifying 
      drug for the treatment of PD.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Youdim, Moussa B H
AU  - Youdim MB
AD  - Technion-Rappaport Faculty of Medicine, Eve Topf and NPF Centers of Excellence 
      for Neurodegenerative Diseases, Haifa, Israel Abital Pharma Pipeline Ltd., Tel 
      Aviv, Israel. Electronic address: Youdim@tx.technion.ac.il.
FAU - Kupershmidt, Lana
AU  - Kupershmidt L
FAU - Amit, Tamar
AU  - Amit T
FAU - Weinreb, Orly
AU  - Weinreb O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Parkinsonism Relat Disord
JT  - Parkinsonism & related disorders
JID - 9513583
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Neuroprotective Agents)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Neuroprotective Agents/*therapeutic use
MH  - Parkinson Disease/*drug therapy
OTO - NOTNLM
OT  - BDNF
OT  - GDNF
OT  - Iron chelator
OT  - Ladostigil
OT  - Limited tyramine potentiation
OT  - M30
OT  - MAO inhibition
OT  - Monoamine oxidase
OT  - Neurogenesis
OT  - Neuroprotection
OT  - Neurorestoration
EDAT- 2013/11/23 06:00
MHDA- 2014/07/12 06:00
CRDT- 2013/11/23 06:00
PHST- 2013/11/23 06:00 [entrez]
PHST- 2013/11/23 06:00 [pubmed]
PHST- 2014/07/12 06:00 [medline]
AID - S1353-8020(13)70032-4 [pii]
AID - 10.1016/S1353-8020(13)70032-4 [doi]
PST - ppublish
SO  - Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S132-6. doi: 
      10.1016/S1353-8020(13)70032-4.