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REVIEW article

Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1546083
This article is part of the Research Topic Reelin in the Synapse: Role in CNS Function and Disease View all articles

Regulatory mechanism of Reelin activity: a platform for exploiting Reelin as a therapeutic agent

Provisionally accepted
  • Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan

The final, formatted version of the article will be published soon.

    Reelin is a secreted glycoprotein that was initially investigated in the field of neuronal development.However, in recent decades, its role in the adult brain has become increasingly important, and it is now clear that diminished Reelin function is involved in the pathogenesis and progression of neuropsychiatric and neurodegenerative disorders, including schizophrenia and Alzheimer's disease (AD). Reelin activity is regulated at multiple steps, including synthesis, posttranslational modification, secretion, oligomerization, proteolytic processing, and interactions with extracellular molecules.Moreover, the differential use of two canonical receptors and the presence of non-canonical receptors and co-receptors add to the functional diversity of Reelin. In this review, I summarize recent findings on the molecular mechanisms of Reelin activity. I also discuss possible strategies to enhance Reelin's function. A complete understanding of Reelin function and its regulatory mechanisms in the adult central nervous system could help ameliorate neuropsychiatric and neurodegenerative disorders.

    Keywords: reelin, ApoER2, VLDLR, Oligomerization, Proteolysis, Alzheimer's disease

    Received: 16 Dec 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Hattori. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mitsuharu Hattori, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Aichi, Japan

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.