Pharmacological approach for targeting dysfunctional brain plasticity: Focus on neural cell adhesion molecule (NCAM).
Brain plasticity refers to the ability of the brain to undergo functionally relevant adaptations in response to external and internal stimuli. Alterations in brain plasticity have been associated with several neuropsychiatric disorders, and current theories suggest that dysfunctions in neuronal circuits and synaptogenesis have a major impact in the development of these diseases. Among the molecules that regulate brain plasticity, neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM have been of particular interest for years because alterations in NCAM and PSA-NCAM levels have been associated with memory impairment, depression, autistic spectrum disorders and schizophrenia. In this review, we discuss the roles of NCAM and PSA-NCAM in the regulation of brain plasticity and, in particular, their roles in the mechanisms of depression. We also demonstrate that the NCAM-mimetic peptides FGL and Enreptin are able to restore disrupted neuronal plasticity. FGL peptide has also been demonstrated to ameliorate the symptoms of depressive-like behavior in NCAM-deficient mice and therefore, may be considered a new drug candidate for the treatment of depression as well as other neuropsychiatric disorders with disrupted neuroplasticity.
Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia. Electronic address: anu.aonurm@ut.ee.
Anu
A
Aonurm-Helm
Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Külli
K
Jaako
Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Monika
M
Jürgenson
Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Alexander
A
Zharkovsky
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001927:Brain Diseases / Q000188:drug therapy* / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism
D002491:Central Nervous System Agents; D019006:Neural Cell Adhesion Molecules
Depression; NCAM-mimetic peptides; Neural cell adhesion molecule