Motoneuronotrophic factor 1 receptor (MNTF1R)

Motoneuronotrophic factor 1 receptor (MNTF1R) is a cell surface receptor complex that mediates the biological activities of Motoneuronotrophic factor 1 (MNTF1), an endogenous 33-amino acid peptide expressed during early human embryonic development [6, 11]. MNTF1 and its synthetic hexapeptide analog, GM6 (Alirinetide), function as master regulators of the nervous system, promoting motoneuron survival, axonal regeneration, and the restoration of cellular homeostasis [8, 12]. The receptor system is characterized by its multi-target nature; MNTF1R signaling involves the positive allosteric modulation of the insulin receptor (IR) and insulin-like growth factor receptors (IGF1R, IGF2R), as well as the activation of Notch and Hedgehog signaling pathways [8, 9, 14]. By engaging these diverse pathways, the target regulates the expression of thousands of genes involved in neuroprotection, anti-inflammatory responses, and the prevention of protein aggregation [15, 32]. MNTF1R is a significant therapeutic target for neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and Parkinson's disease, where it aims to halt disease progression and support neuronal repair [17, 18, 34].

Other names

MNTF receptorMotoneuron trophic factor receptorMNTF1 receptorMotoneuronotrophic factor receptor

Multi-target master regulator; acts as a positive allosteric modulator of the insulin receptor (IR) and insulin-like growth factor receptors (IGF1R, IGF2R); activates Notch and Hedgehog (Patched/Smoothened) signaling pathways; modulates expression of disease-associated genes such as SOD1 and TDP-43.