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The Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is a ligand-gated ion channel that mediates fast excitatory synaptic transmission in the central nervous system [1, 6]. It plays a pivotal role in synaptic plasticity, which is the cellular basis for learning and memory formation [1, 2]. The drug candidate NA-831 (Traneurocin) acts as a positive allosteric modulator of the AMPA receptor, a mechanism that triggers the upregulation of the Brain-Derived Neurotrophic Factor (BDNF) expression pathway [2, 8]. BDNF is a vital neurotrophin that promotes the survival, growth, and differentiation of neurons, particularly in the hippocampus [3, 4]. By enhancing this pathway, NA-831 stimulates adult hippocampal neurogenesis and provides neuroprotection against the cognitive decline associated with neurodegenerative diseases [5, 7]. This approach is currently being investigated for the treatment of Alzheimer's disease, where it aims to restore neuronal health and improve memory functions [9, 10].
Positive allosteric modulation of AMPA receptors leading to increased BDNF expression and subsequent neurogenesis and neuroprotection.
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