A Dichotomous Role for FABP7 in Sleep and Alzheimer’s Disease Pathogenesis: A Hypothesis

• DOI: 10.3389/fnins.2022.798994
• Publication Date: 2022-06-30T09:25:17Z
• Authors: Hope Needham; Grace Torpey; Carlos C. Flores; Christopher J. Davis; William M. Vander...; Jason R. Gerstner
• Keywords: Astrogliosis

Fatty acid binding proteins (FABPs) are a family of intracellular lipid chaperone known to play critical roles in the regulation fatty uptake and transport as well gene expression. Brain-type protein (FABP7) is enriched astrocytes has been implicated sleep/wake neurodegenerative diseases; however, precise mechanisms underlying role FABP7 these biological processes remain unclear. binds both arachidonic (AA) docosahexaenoic (DHA), resulting discrete physiological responses. Here, we propose dichotomous for which ligand type determines subcellular translocation acids, either promoting wakefulness aligned with Alzheimer's pathogenesis or sleep concomitant activation anti-inflammatory pathways neuroprotection. We hypothesize that FABP7-mediated AA endoplasmic reticulum increases astrogliosis, impedes glutamatergic uptake, enhances inflammatory via COX-2 dependent generation pro-inflammatory prostaglandins. Conversely, DHA nucleus stabilizes astrocyte-neuron lactate shuttle dynamics, preserves promotes by activating through peroxisome proliferator-activated receptor-γ transcriptional cascade. Importantly, this model generates several testable hypotheses applicable other diseases, including amyotrophic lateral sclerosis Parkinson's disease.