PMID- 29860423
OWN - NLM
STAT- MEDLINE
DCOM- 20190308
LR  - 20190308
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 27
IP  - 17
DP  - 2018 Sep 1
TI  - Improvement of BDNF signalling by P42 peptide in Huntington's disease.
PG  - 3012-3028
LID - 10.1093/hmg/ddy207 [doi]
AB  - Huntington's disease (HD) is caused by a mutation in the Huntingtin (HTT) 
      protein. We previously reported that the 23aa peptide of HTT protein, P42, is 
      preventing HD pathological phenotypes, such as aggregation, reduction of motor 
      performances and neurodegeneration. A systemic treatment with P42 during the 
      pre-symptomatic phase of the disease showed therapeutic potential in R6/2 mice. 
      We here tested P42 effects when administered during the post-symptomatic phase. 
      The P42 treatment alleviated deficits in motor performances, even when symptoms 
      have already started. Because changes in the level and activity of brain-derived 
      neurotrophic factor (BDNF) have been shown to play a central role in HD, we 
      analysed the influence of P42 on BDNF deficit and associated phenotypes. Our data 
      suggest that P42 is involved in the spatio-temporal control of bdnf and trkB mRNA 
      and their protein levels. Related to this enhancement of BDNF-TrkB signalling, 
      R6/2 mice treated with P42, exhibit reduced anxiety, better learning and memory 
      performances, and better long-term potentiation (LTP) response. Finally we 
      identified a direct influence of P42 peptide on neuronal plasticity and activity. 
      These results suggest that P42 offers an efficient therapeutic potential not only 
      by preventing aggregation of mutant HTT at early stages of the disease, but also 
      by favouring some physiological functions of normal HTT, as P42 is naturally part 
      of it, at the different stages of the disease. This makes P42 peptide potentially 
      suitable not only to prevent, but also to treat HD.
FAU - Couly, Simon
AU  - Couly S
AD  - MMDN, Univ-Montpellier, EPHE, INSERM, UMR-S1198, Montpellier F-34095, France.
FAU - Paucard, Alexia
AU  - Paucard A
AD  - MMDN, Univ-Montpellier, EPHE, INSERM, UMR-S1198, Montpellier F-34095, France.
FAU - Bonneaud, Nathalie
AU  - Bonneaud N
AD  - MMDN, Univ-Montpellier, EPHE, INSERM, UMR-S1198, Montpellier F-34095, France.
FAU - Maurice, Tangui
AU  - Maurice T
AD  - MMDN, Univ-Montpellier, EPHE, INSERM, UMR-S1198, Montpellier F-34095, France.
FAU - Benigno, Lorraine
AU  - Benigno L
AD  - Medesis Pharma, Baillargues F-34670, France.
FAU - Jourdan, Christophe
AU  - Jourdan C
AD  - MMDN, Univ-Montpellier, EPHE, INSERM, UMR-S1198, Montpellier F-34095, France.
FAU - Cohen-Solal, Catherine
AU  - Cohen-Solal C
AD  - IBMM-UMR5247, Univ-Montpellier, Montpellier F-34095, France.
FAU - Vignes, Michel
AU  - Vignes M
AD  - IBMM-UMR5247, Univ-Montpellier, Montpellier F-34095, France.
FAU - Maschat, Florence
AU  - Maschat F
AD  - MMDN, Univ-Montpellier, EPHE, INSERM, UMR-S1198, Montpellier F-34095, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Huntingtin Protein)
RN  - 0 (P42 peptide)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Animals
MH  - Anxiety/*drug therapy/metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Female
MH  - Humans
MH  - Huntingtin Protein/*metabolism
MH  - Huntington Disease/*drug therapy/metabolism/pathology
MH  - Male
MH  - Memory/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred CBA
MH  - Mice, Transgenic
MH  - Peptide Fragments/*pharmacology
MH  - Signal Transduction
EDAT- 2018/06/04 06:00
MHDA- 2019/03/09 06:00
CRDT- 2018/06/04 06:00
PHST- 2018/03/30 00:00 [received]
PHST- 2018/05/23 00:00 [accepted]
PHST- 2018/06/04 06:00 [pubmed]
PHST- 2019/03/09 06:00 [medline]
PHST- 2018/06/04 06:00 [entrez]
AID - 5026425 [pii]
AID - 10.1093/hmg/ddy207 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2018 Sep 1;27(17):3012-3028. doi: 10.1093/hmg/ddy207.