Immature Neurons in the Postnatal Brain: Markers, Modulation, and Involvement in Normal and Aberrant Plasticity.

Cells require constant transcription and translation to maintain function. Given their unique role in brain connectivity, neurons need carefully regulated protein synthesis to perform optimally. Neuronal homeostasis and function demand accurate and efficient transcription, optimal ribosome biogenesis and assembly, and strict regulation of RNA translation. During periods of stress, cellular adaptive pathways selectively regulate RNA translation. One example is by the formation of stress granules [,]. These membraneless complexes of protein, RNA, and translation factors serve many functions, including biomolecule storage, scaffolds for RNA-binding proteins, cell signaling, and the inhibition of translation [,,]. In the early stages of Alzheimer’s disease (AD) and related disorders (ADRD), translation is impaired [,]. Although stress granules colocalize with pathological proteins associated with several neurodegenerative diseases, the mechanisms driving these translational deficits in disease remain elusive. The microtubule-binding protein tau (MAPT) is expressed primarily in the central nervous system but can be found in the pancreas, muscle fibers, smooth muscle cells, and kidneys and serves a key role in neuronal function by stabilizing microtubules [,,,,]. However, tau adopts toxic conformations under various stressors, culminating in the intracellular aggregation of tangles. Pathologically, AD is characterized by the appearance of tau tangles and amyloid-β plaques [,]. Clinically, patients present with impaired memory, struggle with reasoning and decision-making, experience difficulties speaking, an inability to perform normal daily tasks, and changes in personality, leading to social withdrawal []. In 2020, over 55 million people worldwide were diagnosed with AD, and, in 2025, approximately 7.2 million people were living with AD in the United States alone [,].