Understanding the pathogenetic mechanisms underlying altered neuronal function associated with CAMK2B mutations

Rossella Borghi; Marina Trivisano; Nicola Specchio; Marco Tartaglia; Claudia Compagnucci

doi:10.1016/j.neubiorev.2023.105299

Understanding the pathogenetic mechanisms underlying altered neuronal function associated with CAMK2B mutations

Neurosci Biobehav Rev. 2023 Sep:152:105299. doi: 10.1016/j.neubiorev.2023.105299. Epub 2023 Jun 28.

Authors

Rossella Borghi¹, Marina Trivisano², Nicola Specchio², Marco Tartaglia¹, Claudia Compagnucci³

Affiliations

¹ Molecular Genetics and Functional Genomics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
² Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesu' Children's Hospital, IRCCS, Rome, Italy.
³ Molecular Genetics and Functional Genomics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. Electronic address: claudia.compagnucci@opbg.net.

PMID: 37391113
DOI: 10.1016/j.neubiorev.2023.105299

Abstract

'Dominant mutations in CAMK2B, encoding a subunit of the calcium/calmodulin-dependent protein kinase II (CAMK2), a serine/threonine kinase playing a key role in synaptic plasticity, learning and memory, underlie a recently characterized neurodevelopmental disorder (MRD54) characterized by delayed psychomotor development, mild to severe intellectual disability, hypotonia, and behavioral abnormalities. Targeted therapies to treat MRD54 are currently unavailable. In this review, we revise current knowledge on the molecular and cellular mechanisms underlying the altered neuronal function associated with defective CAMKIIβ function. We also summarize the identified genotype-phenotype correlations and discuss the disease models that have been generated to profile the altered neuronal phenotype and understand the pathophysiology of this disease.

Keywords: CAMK2B; Calcium influx; Mechanism of disease; Neurodevelopment; Neuronal morphology and function.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Calcium-Calmodulin-Dependent Protein Kinase Type 2* / genetics
Calcium-Calmodulin-Dependent Protein Kinase Type 2* / metabolism
Humans
Intellectual Disability / genetics
Learning
Mutation / genetics
Neurodevelopmental Disorders / metabolism
Neuronal Plasticity
Neurons* / physiology

Substances

Calcium-Calmodulin-Dependent Protein Kinase Type 2
CAMK2B protein, human