Alcohol use disorder disrupts BDNF maturation via the PAI-1 pathway which could be reversible with abstinence.
Brain-Derived Neurotrophic Factor
/ blood
Humans
Alcoholism
/ metabolism
Plasminogen Activator Inhibitor 1
/ metabolism
Male
Adult
Tissue Plasminogen Activator
/ metabolism
Female
Signal Transduction
Receptors, Nerve Growth Factor
/ metabolism
Middle Aged
Receptor, trkB
/ metabolism
Alcohol Abstinence
Protein Precursors
/ metabolism
Membrane Glycoproteins
Nerve Tissue Proteins
Abstinence treatment
Alcohol use disorder (AUD)
Mature brain-derived neurotrophic factor (mBDNF)
Plasminogen activator inhibitor-1 (PAI-1)
Pro-brain-derived neurotrophic factor (ProBDNF)
Tissue plasminogen activator (tPA)
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 Sep 2024
27 Sep 2024
Historique:
received:
08
05
2024
accepted:
17
09
2024
medline:
28
9
2024
pubmed:
28
9
2024
entrez:
27
9
2024
Statut:
epublish
Résumé
The plasminogen activator inhibitor-1 (PAI-1)→mature brain-derived neurotrophic factor (mBDNF) pathway plays a pivotal role in the conversion of probrain-BDNF (ProBDNF) to mBDNF, but its clinical relevance in patients with alcohol use disorder (AUD) remains unknown. Enzyme-linked immunosorbent assays were used to examine the relevant protein levels of components of the PAI-1→mBDNF pathway in plasma samples from three groups of subjects, and statistical analysis was performed using analysis of variance (ANOVA) and one-way repeated-measures ANOVA. Our findings revealed significant alterations induced by alcohol. (1) AUD was associated with significant decreases in tissue plasminogen activator (tPA), mBDNF, and tropomyosin receptor kinase B (TrkB); significant increases in PAI-1, ProBDNF, and P75 neurotrophin receptor (P75NTR); and inhibited conversion of ProBDNF to mBDNF. (2) Following abstinence, the levels of tPA, mBDNF, and TrkB in the AUD group significantly increased, whereas the levels of PAI-1, ProBDNF, and P75NTR significantly decreased, promoting the conversion of ProBDNF to mBDNF. These clinical outcomes collectively suggest that AUD inhibits the conversion of ProBDNF to mBDNF and that abstinence reverses this process. The PAI-1→mBDNF cleavage pathway is hypothesized to be associated with AUD and abstinence treatment.
Identifiants
pubmed: 39333668
doi: 10.1038/s41598-024-73347-2
pii: 10.1038/s41598-024-73347-2
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
Plasminogen Activator Inhibitor 1
0
BDNF protein, human
7171WSG8A2
Tissue Plasminogen Activator
EC 3.4.21.68
SERPINE1 protein, human
0
Receptors, Nerve Growth Factor
0
Receptor, trkB
EC 2.7.10.1
NGFR protein, human
0
tropomyosin-related kinase-B, human
EC 2.7.10.1
Protein Precursors
0
Membrane Glycoproteins
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22150Subventions
Organisme : Jinhua Key Science and Technology Program Projects
ID : 2023-3-154 and 2023-3-157
Organisme : Jinhua Key Science and Technology Program Projects
ID : 2023-3-154 and 2023-3-157
Informations de copyright
© 2024. The Author(s).
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