PMID- 12794311
OWN - NLM
STAT- MEDLINE
DCOM- 20030818
LR  - 20220410
IS  - 0895-8696 (Print)
IS  - 0895-8696 (Linking)
VI  - 20
IP  - 2
DP  - 2003 Apr
TI  - MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity 
      for dopaminergic neurons.
PG  - 173-88
AB  - We describe the discovery of a novel, 20 kDa, secreted human protein named 
      mesencephalic astrocyte-derived neurotrophic factor, or MANF. The homologous, 
      native molecule was initially derived from a rat mesencephalic type-1 astrocyte 
      cell line and recombinant MANF subcloned from a cDNA encoding human arginine-rich 
      protein. MANF selectively protects nigral dopaminergic neurons, versus GABAergic 
      or serotonergic neurons. The discovery of MANF marks a more systematic approach 
      in the search for astrocyte-derived, secreted proteins that selectively protect 
      specific neuronal phenotypes. Compared to glial cell line-derived neurotrophic 
      factor (GDNF) and brain-derived neurotrophic factor (BDNF), MANF was more 
      selective in the protection of dopaminergic neurons at lower (0.05-0.25 ng/mL) 
      and middle (0.5-2.5 ng/mL) concentrations: MANF>GDNF>BDNF. GDNF was more 
      selective at higher concentrations (25-50 ng/ml): GDNF>MANF>BDNF. Two domains in 
      MANF of 39-AA and 109-AA respectively, and eight cysteines are conserved from C. 
      elegans to man. MANF is encoded by a 4.3 Kb gene with 4 exons, and is located on 
      the short arm of human chromosome 3. The secondary structure is dominated by 
      alpha-helices (47%) and random coils (37%). Studies to determine the localization 
      of MANF in the brains of rat, monkey, and man, as well as the receptor, signaling 
      pathways, and biologically active peptide mimetics are in progress. The 
      selective, neuroprotective effect of MANF for dopaminergic neurons suggests that 
      it may be indicated for the treatment of Parkinson's disease.
FAU - Petrova, Penka
AU  - Petrova P
AD  - Laboratories of Protein Chemistry, Molecular Biology & Cell Biology, Prescient 
      NeuroPharma Inc., 96 Skyway Avenue, Toronto, Ontario, Canada M9W 4Y9.
FAU - Raibekas, Andrei
AU  - Raibekas A
FAU - Pevsner, Jonathan
AU  - Pevsner J
FAU - Vigo, Noel
AU  - Vigo N
FAU - Anafi, Mordechai
AU  - Anafi M
FAU - Moore, Mary K
AU  - Moore MK
FAU - Peaire, Amy E
AU  - Peaire AE
FAU - Shridhar, Viji
AU  - Shridhar V
FAU - Smith, David I
AU  - Smith DI
FAU - Kelly, John
AU  - Kelly J
FAU - Durocher, Yves
AU  - Durocher Y
FAU - Commissiong, John W
AU  - Commissiong JW
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DNA, Complementary)
RN  - 0 (GDNF protein, human)
RN  - 0 (Gdnf protein, rat)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (MANF protein, human)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Amino Acid Sequence/genetics
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Base Sequence/genetics
MH  - Brain-Derived Neurotrophic Factor/metabolism/pharmacology
MH  - Cell Line, Transformed
MH  - DNA, Complementary/analysis/genetics
MH  - Dopamine/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Humans
MH  - Mesencephalon/cytology/*metabolism
MH  - Molecular Sequence Data
MH  - Nerve Growth Factors/genetics/*isolation & purification/metabolism/pharmacology
MH  - Nerve Tissue Proteins/genetics/*isolation & purification
MH  - Neurons/drug effects/*metabolism
MH  - Neuroprotective Agents/*isolation & purification/pharmacology
MH  - Parkinson Disease/drug therapy/genetics
MH  - Rats
EDAT- 2003/06/10 05:00
MHDA- 2003/08/19 05:00
CRDT- 2003/06/10 05:00
PHST- 2003/06/10 05:00 [pubmed]
PHST- 2003/08/19 05:00 [medline]
PHST- 2003/06/10 05:00 [entrez]
AID - JMN:20:2:173 [pii]
AID - 10.1385/jmn:20:2:173 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2003 Apr;20(2):173-88. doi: 10.1385/jmn:20:2:173.