Disrupted RNA‐networks in Alzheimer’s disease

Synapse loss is well‐documented and underlies cognitive decline in Alzheimer’s disease (AD) and other comorbid neuropsychiatric disorders such as depression. To date, few molecular targets and mechanisms are identified to restore/maintain healthy synapses in AD. AD and depression both have disrupted mechanistic/mammalian target of rapamycin complex 1 (mTORC1) activity. Since mTORC1 is involved in protein synthesis, disruptions in mTORC1 activity creates an imbalance between mRNA translation and repression at synapses. We have demonstrated that mTORC1 signaling is overactive in the prefrontal cortex (PFC) of AD patients and animal models. RNA binding proteins (RBP) are significant regulators of mRNA translation. A single RBP can bind to multiple mRNAs to either enhance or repress their translation. Dysregulated expression of RBPs can thus lead to imbalanced mRNA translation and protein synthesis.