Table 2.

Mechanisms of neuronal damage, and possible beneficial effects of 5-HT₇ receptors agonism

Neurodegeneration mechanism	5-HT7 possible role	References
Excitotoxicity	Activation of MAPK/ERK and PI3/Akt/GSK3b protects against glutamate-induced damage Decreased expression of NR2B and NR1 subunits of NMDA glutamate receptors Increased expression of superoxide dismutase and glutathione	Jiang et al. (2000); Pi et al. (2004); Li et al. (2005) Vasefi et al. (2013a) Yuksel et al. (2019)
Oxidative stress	No study evaluated effect in the CNS In a sepsis-induced lung injury, 5-HT7 receptor agonism decreased ROS burden 5-HT7 antagonism decreased oxidative burden in bleomycin-induced pulmonary fibrosis 5-HT7 activation enhances microsome stability towards oxidative metabolism (Lacivita et al., 2016a) ERK and Akt protect PC12 cells from oxidative damage	Cadirci et al. (2013) Tawfik and Makary (2017) Lacivita et al. (2016a) Ong et al. (2016)
Apoptosis	5-HT7 receptor agonism reduces apoptosis in the streptozotocin-induced AD model	Hashemi-Firouzi et al. (2017)
Long term depression/ potentiation impairment	5-HT7 KO mice display LTP impairment 5-HT7 agonism reduces mGluR-dependent LTD	Roberts et al. (2004) Costa et al. (2012)
Synaptic impairment	5-HT7 agonism increases dendritic density and synaptogenesis in the cortical and striatal forebrain 5-HT7 agonism induces dendritic sprouting and neurite enlargement	Speranza et al. (2013, 2015, 2017) Kvachnina et al. (2005); Canese et al. (2015)
Neurotrophin depletion	5-HT7 agonism increases PDGF-β 5-HT7 agonism increases the expression and affinity of trk-B	Vasefi et al. (2013b) Samarajeewa et al. (2014)