PMID- 23135810
OWN - NLM
STAT- MEDLINE
DCOM- 20130523
LR  - 20131121
IS  - 1521-3765 (Electronic)
IS  - 0947-6539 (Linking)
VI  - 18
IP  - 49
DP  - 2012 Dec 3
TI  - Copper, BDNF and Its N-terminal domain: inorganic features and biological 
      perspectives.
PG  - 15618-31
LID - 10.1002/chem.201202775 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin that influences 
      development, maintenance, survival, and synaptic plasticity of central and 
      peripheral nervous systems. Altered BDNF signaling is involved in several 
      neurodegenerative disorders including Alzheimer's disease. Metal ions may 
      influence the BDNF activity and it is well known that the alteration of Cu(2+) 
      homeostasis is a prominent factor in the development of neurological pathologies. 
      The N-terminal domain of BDNF represents the recognition site of its specific 
      receptor TrkB, and metal ions interaction with this protein domain may influence 
      the protein/receptor interaction. In spite of this, no data inherent the 
      interaction of BDNF with Cu(2+) ions has been reported up to now. Cu(2+) 
      complexes of the peptide fragment BDNF(1-12) encompassing the sequence 1-12 of 
      N-terminal domain of human BDNF protein were characterized by means of 
      potentiometry, spectroscopic methods (UV/Vis, CD, EPR), parallel tempering 
      simulations and DFT-geometry optimizations. Coordination features of the 
      acetylated form, Ac-BDNF(1-12), were also characterized to understand the 
      involvement of the terminal amino group. Whereas, an analogous peptide, 
      BDNF(1-12)D3N, in which the aspartate residue was substituted by an asparagine, 
      was synthesized to provide evidence on the possible role of carboxylate group in 
      Cu(2+) coordination. The results demonstrated that the amino group is involved in 
      metal binding and the metal coordination environment of the predominant complex 
      species at physiological pH consisted of one amino group, two amide nitrogen 
      atoms, and one carboxylate group. Noteworthy, a strong decrease of the 
      proliferative activity of both BDNF(1-12) and the whole protein on a SHSY5Y 
      neuroblastoma cell line was found after treatment in the presence of Cu(2+). The 
      effect of metal addition is opposite to that observed for the analogous fragment 
      of nerve growth factor (NGF) protein, highlighting the role of specific domains, 
      and suggesting that Cu(2+) may drive different pathways for the BDNF and NGF in 
      physiological as well as pathological conditions.
CI  - Copyright (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Travaglia, Alessio
AU  - Travaglia A
AD  - Dipartimento di Scienze Chimiche, Universita degli Studi di Catania, Italy.
FAU - La Mendola, Diego
AU  - La Mendola D
FAU - Magri, Antonio
AU  - Magri A
FAU - Nicoletti, Vincenzo Giuseppe
AU  - Nicoletti VG
FAU - Pietropaolo, Adriana
AU  - Pietropaolo A
FAU - Rizzarelli, Enrico
AU  - Rizzarelli E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121107
PL  - Germany
TA  - Chemistry
JT  - Chemistry (Weinheim an der Bergstrasse, Germany)
JID - 9513783
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Peptide Fragments)
RN  - 789U1901C5 (Copper)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Circular Dichroism
MH  - Copper/*chemistry/*metabolism
MH  - Humans
MH  - Nerve Growth Factor/*chemistry/*metabolism
MH  - Peptide Fragments/*chemistry/metabolism
MH  - Spectrophotometry, Ultraviolet
EDAT- 2012/11/09 06:00
MHDA- 2013/05/25 06:00
CRDT- 2012/11/09 06:00
PHST- 2012/08/01 00:00 [received]
PHST- 2012/11/09 06:00 [entrez]
PHST- 2012/11/09 06:00 [pubmed]
PHST- 2013/05/25 06:00 [medline]
AID - 10.1002/chem.201202775 [doi]
PST - ppublish
SO  - Chemistry. 2012 Dec 3;18(49):15618-31. doi: 10.1002/chem.201202775. Epub 2012 Nov 
      7.