PMID- 16890384
OWN - NLM
STAT- MEDLINE
DCOM- 20070130
LR  - 20061106
IS  - 0306-9877 (Print)
IS  - 0306-9877 (Linking)
VI  - 68
IP  - 1
DP  - 2007
TI  - The P11, tPA/plasminogen system and brain-derived neurotrophic factor: 
      Implications for the pathogenesis of major depression and the therapeutic 
      mechanism of antidepressants.
PG  - 180-3
AB  - Major depressive disorder (MDD) is a common disabling psychiatric illness with an 
      unknown etiology. Evidence from animal and human studies suggests that a 
      disturbance in serotonergic (5-HT) activity and/or brain-derived neurotrophic 
      factor (BDNF) signaling may be implicated in the pathogenesis of MDD. Recently, a 
      protein, p11, has been found to increase the number of 5-HT(1B) receptors on the 
      surface of cells and enhance 5-HT(1B) receptor function. Furthermore, mice 
      over-expressing p11 acted as if they were undergoing treatment with 
      antidepressants and p11 knockout mice exhibit a depression-like phenotype and 
      reduced behavioural reactions to an antidepressant. As tissue-type plasminogen 
      activator (tPA)/plasminogen proteolytic cascade is implicated in the cleavage of 
      proBDNF to BDNF, and p11, a component of the Annexin II, which can greatly 
      enhance the activation of plasmin by tPA, it is proposed that p11 may act through 
      the tPA/plasminogen/BDNF pathway to achieve its antidepressant effect. Attempts 
      to confirm this hypothesis may lead to new directions in the study of the 
      pathogenesis of MDD and the development of a novel intervention for this 
      disorder. In addition, BDNF is also implicated in several psychiatric diseases 
      such as schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder 
      and Alzheimer's disease; whether p11 and other components related to the 
      tPA/plasminogen pathway may be related to the pathogenesis of these diseases 
      needs further exploration.
FAU - Tsai, Shih-Jen
AU  - Tsai SJ
AD  - Department of Psychiatry, Taipei Veterans General Hospital and Division of 
      Psychiatry, School of Medicine, National Yang-Ming University, No. 201 Shih-Pai 
      Road, Sec. 2, 11217 Taipei, Taiwan. sjtsai@vghtpe.gov.tw
LA  - eng
PT  - Journal Article
DEP - 20060804
PL  - United States
TA  - Med Hypotheses
JT  - Medical hypotheses
JID - 7505668
RN  - 0 (Annexin A2)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptor, Serotonin, 5-HT1B)
RN  - 0 (S100 Proteins)
RN  - 0 (S100 calcium binding protein A10)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Annexin A2/*metabolism
MH  - Antidepressive Agents/*administration & dosage
MH  - Brain/drug effects/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Depressive Disorder, Major/*drug therapy/*metabolism
MH  - Humans
MH  - Models, Neurological
MH  - Receptor, Serotonin, 5-HT1B/metabolism
MH  - S100 Proteins/*metabolism
MH  - Tissue Plasminogen Activator/*metabolism
EDAT- 2006/08/08 09:00
MHDA- 2007/01/31 09:00
CRDT- 2006/08/08 09:00
PHST- 2006/05/28 00:00 [received]
PHST- 2006/06/02 00:00 [accepted]
PHST- 2006/08/08 09:00 [pubmed]
PHST- 2007/01/31 09:00 [medline]
PHST- 2006/08/08 09:00 [entrez]
AID - S0306-9877(06)00437-3 [pii]
AID - 10.1016/j.mehy.2006.06.005 [doi]
PST - ppublish
SO  - Med Hypotheses. 2007;68(1):180-3. doi: 10.1016/j.mehy.2006.06.005. Epub 2006 Aug 
      4.