PMID- 23382994
OWN - NLM
STAT- MEDLINE
DCOM- 20130719
LR  - 20220318
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 1
DP  - 2013
TI  - Neurotrophic and neuroprotective actions of (-)- and (+)-phenserine, candidate 
      drugs for Alzheimer's disease.
PG  - e54887
LID - 10.1371/journal.pone.0054887 [doi]
LID - e54887
AB  - Neuronal dysfunction and demise together with a reduction in neurogenesis are 
      cardinal features of Alzheimer's disease (AD) induced by a combination of 
      oxidative stress, toxic amyloid-beta peptide (Abeta) and a loss of trophic factor 
      support. Amelioration of these was assessed with the Abeta lowering AD experimental 
      drugs (+)-phenserine and (-)-phenserine in neuronal cultures, and actions in mice 
      were evaluated with (+)-phenserine. Both experimental drugs together with the 
      metabolite N1-norphenserine induced neurotrophic actions in human SH-SY5Y cells 
      that were mediated by the protein kinase C (PKC) and extracellular 
      signal-regulated kinases (ERK) pathways, were evident in cells expressing amyloid 
      precursor protein Swedish mutation (APP(SWE)), and retained in the presence of Abeta 
      and oxidative stress challenge. (+)-Phenserine, together with its (-) enantiomer 
      as well as its N1- and N8-norphenserine and N1,N8-bisnorphenserine metabolites, 
      likewise provided neuroprotective activity against oxidative stress and glutamate 
      toxicity via the PKC and ERK pathways. These neurotrophic and neuroprotective 
      actions were evident in primary cultures of subventricular zone (SVZ) neural 
      progenitor cells, whose neurosphere size and survival were augmented by 
      (+)-phenserine. Translation of these effects in vivo was assessed in wild type 
      and AD APPswe transgenic (Tg2576) mice by doublecortin (DCX) immunohistochemical 
      analysis of neurogenesis in the SVZ, which was significantly elevated by 16 day 
      systemic (+)-phenserine treatment, in the presence of a (+)-phenserine-induced 
      elevation in brain- derived neurotrophic factor (BDNF).
FAU - Lilja, Anna M
AU  - Lilja AM
AD  - Alzheimer Neurobiology Center, Department of Neurobiology, Care Sciences and 
      Society, Karolinska Institutet, Karolinska University Hospital Huddinge, 
      Stockholm, Sweden. anna.lilja@ki.se
FAU - Luo, Yu
AU  - Luo Y
FAU - Yu, Qian-sheng
AU  - Yu QS
FAU - Rojdner, Jennie
AU  - Rojdner J
FAU - Li, Yazhou
AU  - Li Y
FAU - Marini, Ann M
AU  - Marini AM
FAU - Marutle, Amelia
AU  - Marutle A
FAU - Nordberg, Agneta
AU  - Nordberg A
FAU - Greig, Nigel H
AU  - Greig NH
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130130
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Dcx protein, mouse)
RN  - 0 (Doublecortin Protein)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - 9U1VM840SP (Physostigmine)
RN  - SUE285UG3S (phenserine)
SB  - IM
MH  - Alzheimer Disease/*drug therapy
MH  - Amyloid beta-Peptides/pharmacology
MH  - Amyloid beta-Protein Precursor/genetics/metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Doublecortin Protein
MH  - Drug Discovery
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation
MH  - Neural Stem Cells/cytology/drug effects/metabolism
MH  - Neurons/cytology/drug effects/metabolism
MH  - Neuroprotective Agents/*chemistry/*pharmacology/therapeutic use
MH  - Oxidative Stress/drug effects
MH  - Peptide Fragments/pharmacology
MH  - Physostigmine/*analogs & derivatives/chemistry/pharmacology/therapeutic use
MH  - Stereoisomerism
PMC - PMC3559887
COIS- Competing Interests: This study was partly funded by a Karolinska Institutet 
      agreement with Johnson & Johnson. There are no patents, products in development 
      or marketed products to declare. This does not alter the authors' adherence to 
      all the PLOS ONE policies on sharing data and materials, as detailed online in 
      the guide for authors.
EDAT- 2013/02/06 06:00
MHDA- 2013/07/20 06:00
PMCR- 2013/01/30
CRDT- 2013/02/06 06:00
PHST- 2012/09/03 00:00 [received]
PHST- 2012/12/17 00:00 [accepted]
PHST- 2013/02/06 06:00 [entrez]
PHST- 2013/02/06 06:00 [pubmed]
PHST- 2013/07/20 06:00 [medline]
PHST- 2013/01/30 00:00 [pmc-release]
AID - PONE-D-12-26906 [pii]
AID - 10.1371/journal.pone.0054887 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(1):e54887. doi: 10.1371/journal.pone.0054887. Epub 2013 Jan 30.