Molecular characterization of NS-1 with robust growth and enhanced phenotypic properties

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Basic research for neurodegenerative disease largely relies on cell line studies, which also act as the primary platform for drug screening in translational medicine. Neuroscreen-1 (NS-1), is a sub-clone of PC12, a noradrenergic cell line that shows dopaminergic properties are widely used in neurobiology, neurotoxicology, and drug discovery studies [1,2]. 1,2

Differentiation of PC12 by NGF is well documented. NGF treatment on PC12 cell leads to cessation of cell division, induction of neurite outgrowth, and production of electrically excitable cells in culture, mimicking the characteristics of sympathetic-like neurons[6] 6. In addition to the neuroprotective and neuro-restorative properties of NGF, dysregulation in NGF signaling has been positively correlated with Alzheimer’s disease (AD)[7] 7, epilepsy[9] 9, and cancer[12] 12. AD is characterized by death of forebrain cholinergic neurons, resulting from imbalance in expression of NGF, Pro NGF, TrkA, p75NTR ( Mufson 2008). NGF regulates proliferation and differentiation of neuronal cells via activation of tyrosine protein kinase (TrkA) receptor, and downstream signaling molecules that include Ras/MAP kinase cascade, IP3-dependent Ca2+ release, and PI3K/Akt pathways[13] 13. Furthermore, NGF increases expression of ChAT and VAChT, cholinergic markers are required for cholinergic neurotransmission[14,15] 14,15. ChAT enables the synthesis of acetylcholine (ACh) from acetyl-CoA and choline, whereas VAChT acts as a membrane transporter loading ACh into secretory vesicle and makes it available for secretion[16] 16. Decrease in ChAT and VAChT is suggested to play a role in the progression of AD[17,18] 17,18.

Muscarinic acetyl choline receptors (Chrms) GPCR found in the cholinergic system signal through binding of acetylcholine and are involved in learning and memory[19,20] 20, and thus been implicated in neuronal diseases [22], [23] [24] 22,23. Similarly, adenosine receptors (AR) mediates the actions of adenosine in CNS by release of neurotransmitters and synaptic plasticity[25] 25. Among four members, A1 receptor is prevalent in the synaptic regions whereas A2A receptor is localized in the striatum and olfactory bulb[26] 26.

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