PMID- 25563591
OWN - NLM
STAT- MEDLINE
DCOM- 20150715
LR  - 20190911
IS  - 1873-5592 (Electronic)
IS  - 1389-4501 (Linking)
VI  - 16
IP  - 1
DP  - 2015
TI  - Oxidative stress and neurodegenerative diseases: a neurotrophic approach.
PG  - 20-30
AB  - Neurotrophins are important neurotrophic factors involved in the survival, 
      differentiation and function of a wide variety of neuron populations. A common 
      feature for most neurotrophins is that they are synthesized as precursor proteins 
      (pro-neurotrophins) that upon being processed by proteolysis render the mature 
      active form responsible for most of their trophic functions. However, some of the 
      pro-neurotrophin form of these proteins, such as the precursor form of NGF 
      (pro-NGF), have been shown to induce opposite effects and trigger apoptosis on 
      neurons through the p75NTR receptor. This suggests that the balance between the 
      levels of proneurotrophin and neurotrophin must be tightly controlled. In this 
      context, it has been shown that in conditions of oxidative stress due for 
      instance to aging or the development of some neurodegenerative disease, 
      neurotrophins are oxidatively modified at least by advanced 
      glycation/lipoxidation end products (AGE/ALEs) which makes pro-NGF refractary to 
      be processed. The lack of maturation and the imbalance in favor of the precursor 
      form may change the pattern of active signaling pathways towards cell death, thus 
      exacerbating the deleterious alterations, for instance during the development of 
      neurodegenerative diseases. Besides that, AGE/ALEs also induce the processing of 
      the pro-NGF receptor p75NTR by alpha- secretase which is followed by the processing 
      by gamma -secretase and the release of the intracellular domain of p75NTR 
      (p75NTRICD). Once cleaved, p75NTRICD recruits two intracellular interactors, NRIF 
      and TRAF6, which allows NRIF phosphorylation by JNK. The phosphorylated form of 
      NRIF then translocates to the nucleus and induces the expression of pro-apoptotic 
      proteins. In this chapter we will summarize the mechanisms by which ROS- induce 
      protein modifications, which proteins are susceptible to be modified, how these 
      modifications affect function and signaling and, finally, how they can be related 
      to neurodegenerative diseases.
FAU - Espinet, Carme
AU  - Espinet C
FAU - Gonzalo, Hugo
AU  - Gonzalo H
FAU - Fleitas, Catherine
AU  - Fleitas C
FAU - Menal, Maria Jose
AU  - Menal MJ
FAU - Egea, Joaquim
AU  - Egea J
AD  - Molecular and Developmental Neurobiology, Dept. Ciencies Mediques Basiques, 
      Facultat de Medicina, Universitat de Lleida/IRBLLEIDA, Rovira Roure 80, 25198, 
      Lleida, Spain. carme.espinet@cmb.udl.cat.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Targets
JT  - Current drug targets
JID - 100960531
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Protein Degradation End Products)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Nerve Growth Factor)
SB  - IM
MH  - Animals
MH  - Glycation End Products, Advanced/metabolism
MH  - Humans
MH  - Nerve Growth Factors/*metabolism
MH  - Neurodegenerative Diseases/*metabolism
MH  - *Oxidative Stress
MH  - Protein Degradation End Products/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Nerve Growth Factor/*metabolism
MH  - Signal Transduction
EDAT- 2015/01/08 06:00
MHDA- 2015/07/16 06:00
CRDT- 2015/01/08 06:00
PHST- 2014/09/16 00:00 [received]
PHST- 2014/10/28 00:00 [revised]
PHST- 2015/01/01 00:00 [accepted]
PHST- 2015/01/08 06:00 [entrez]
PHST- 2015/01/08 06:00 [pubmed]
PHST- 2015/07/16 06:00 [medline]
AID - CDT-EPUB-64377 [pii]
AID - 10.2174/1389450116666150107153233 [doi]
PST - ppublish
SO  - Curr Drug Targets. 2015;16(1):20-30. doi: 10.2174/1389450116666150107153233.