Reelin in the Synapse: Role in CNS Function and Disease

Reelin is a unique glycoprotein that stands at the intersection of neurodevelopment and synaptic function and neuroinflammation. Early in development, Reelin regulates neuronal migration, brain lamination, and cell-cell interactions, while in the mature brain, Reelin modulates synaptic plasticity through the maturation of postsynaptic dendrites, regulation of neurotransmitter release, and glutamate receptor signaling. Additionally, research has shown that circulating Reelin increases in different neuroinflammatory conditions such as multiple sclerosis (MS). Reelin signaling through ApoER2 affects translation and influences the cleavage and processing of APP, ultimately affecting Aβ production and synaptic function. Reelin mutations have been shown to be causal in lissencephaly and temporal lobe epilepsy, impact disease severity in schizophrenia and bipolar disorder, and most recently a rare Reelin variant has been identified that is protective against Alzheimer’s. These genetic links highlight the importance of Reelin signaling throughout the lifespan. This Research Topic brings together a variety of manuscripts reflecting on mechanistic and clinical research into the role of Reelin in normal CNS function and neurologic disease.

Reelin signaling is important for brain development, mature brain function, and the pathogenesis of various Neurological diseases. Many researchers are studying this important protein in their field of interest. Reelin and its receptors ApoER2 and VLDLR affect synaptic function, protein processing, and neuroinflammation, fields that don’t necessarily cross-pollinate unless we look into common mechanisms that bind them all together such as endolysosomal cargo transport or shared signaling mechanisms. This research topic seeks to bring together a variety of perspectives on Reelin and its receptor ApoER2 function to provide a broader insight into the mechanisms of disease and to focus a goal towards therapeutic development.

The scope of the Research Topic should include specific themes such as the role of Reelin and its receptors in regulation of proteolytic processing and the fate of normal and pathogenic proteins such as Amyloid Precursor Protein (APP) and FMRP(Fragile X Mental Retardation Protein), particularly in the context of neurodegenerative diseases like Alzheimer's disease, schizophrenia and autism; the genetic and epigenetic regulation of Reelin expression; and the potential of Reelin as a biomarker or therapeutic target for neurological and inflammatory diseases. The types of manuscripts sought could include original research articles, reviews, mini-reviews, hypotheses, and opinion articles addressing these themes.