RT Journal Article
SR Electronic
T1 Proteomic changes induced by harmine in human brain organoids reveal signaling pathways related to neuroprotection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.16.448740
DO 10.1101/2021.06.16.448740
A1 Karmirian, Karina
A1 Goto-Silva, Lívia
A1 Nascimento, Juliana Minardi
A1 Costa, Marcelo N.
A1 Salerno, José Alexandre
A1 Ornelas, Isis Moraes
A1 Vanderborght, Bart
A1 Martins-de-Souza, Daniel
A1 Rehen, Stevens
YR 2021
UL http://biorxiv.org/content/early/2021/06/17/2021.06.16.448740.abstract
AB Harmine is a β-carboline found in Banisteriopsis caapi, a constituent of ayahuasca brew. Ayahuasca is consumed as a beverage in native Americans’ sacred rituals and in religious ceremonies in Brazil. Throughout the years, the beneficial effects of ayahuasca to improve mental health and life quality have been reported, which propelled the investigation of its therapeutic potential to target neurological disorders such as depression and anxiety. Indeed, antidepressant effects of ayahuasca have been described, raising the question of which cellular mechanisms might underlie those effects. Previous animal studies describe potential neuroprotective mechanisms of harmine, including anti-inflammatory and antioxidant activities, and neurotrophin signaling activation. However, the cellular and molecular mechanisms modulated by harmine in human models remain less investigated. Here we analyzed the short-term changes in the proteome of human brain organoids treated with harmine using shotgun mass spectrometry. Harmine upregulates proteins related to synaptic vesicle cycle, cytoskeleton-dependent intracellular transport, cell cycle, glucose transporter-4 translocation, and neurotrophin signaling pathway. In addition, protein expression levels of Akt and phosphorylated CREB were increased after 24 hour-treatment. Our results shed light on the potential mechanisms that may underlie harmine-induced neuroprotective effects.Competing Interest StatementThe authors have declared no competing interest.