Citation Feature: A new connection between T30 and the mTOR pathway!

Our MAP2 antibody was used in Scientific Reports to demonstrate a novel connection between the mTOR pathway and ⍺7 nAChR signaling via the treatment of hippocampal neurons with T30!

The human acetylcholinesterase C-terminal T30 peptide activates neuronal growth through alpha 7 nicotinic acetylcholine receptors and the mTOR pathway
Graur A, Sinclair P, Schneeweis AK, Pak DT, Kabbani N. Sci Rep. 2023 Jul 15;13(1):11434. PMID: 37454238

T30 is a derivative of the AChE enzyme that has implications in neuronal growth.

The T30 peptide is derived from the C-terminal region of the human acetylcholinesterase enzyme. Its influence extends beyond its conventional enzymatic role because it exhibits the ability to influence neuronal growth by interacting with ⍺7 nicotinic acetylcholine receptors (nAChRs). This interaction can trigger a series of signaling events that contribute to the activation of neuronal growth pathways such as mTOR (mammalian target of rapamycin). The mTOR pathway is a central regulator of various cellular processes, including protein synthesis, cell growth, and cell proliferation. This featured paper from Scientific Reports suggests a new mechanism through which acetylcholinesterase, and its derivative T30, traditionally known for its role in neurotransmission, can influence broader cellular functions.

The effect of T30 can be studied using cultured human neuroblastoma cells.

The study explored how T30 impacts signaling using the human neural cholinergic cell line SH-SY5Y - a model for Alzheimer’s Disease (AD) and known to endogenously express ⍺7 nAChRs. The impact of T30 on neuronal growth was tested at 1 nM, 100 nM, and 1 μM corresponding to low, medium, and high non-toxic levels. In these experiments, neurons were treated with various T30 concentrations for 5 days in-vitro and then immunostained with our anti-MAP2 antibody to visualize dendritic arbors.

T30's influence is dose-dependent.

T30 treatment clearly increased dendritic growth relative to controls. However, the dose-related actions of T30 were also evident, with significant growth observed at 1 nM and 100 nM but a diminished growth effect at 1 μM concentration, an observation seen across two forms of morphometric analyses.

MAP2 stained neurons

T30 promotes dendritic growth in hippocampal neurons. Representative images of anti-MAP2 immunolabeled neurons at 5 DIV of T30 treatment.

T30 as a therapeutic target is an exciting topic for future studies.

The results of this study indicate that T30 promotes neural cell growth through a mechanism of activating α7 nAChRs, and leading to mTOR pathway signaling. The role that these findings play in neural development and disease should be a goal for future studies!