Proteomic changes induced by harmine in human brain organoids reveal signaling pathways related to neuroprotection
OpenAlex – June 17, 2021
Source: OpenAlex
Summary
Harmine, a compound in ayahuasca, shows promise for neuroprotection, particularly in mental health. In a study using human brain organoids (sample size not specified), harmine treatment led to significant upregulation of proteins involved in synaptic function and neurotrophin signaling. Notably, levels of Akt and phosphorylated CREB increased after just 24 hours. These findings suggest that harmine may enhance cellular mechanisms linked to brain health, potentially offering new avenues for treating neurological disorders like depression and anxiety.
Abstract
Abstract 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.