Protein Kinase A in neurological disorders

  • J Neurodev Disord. 2024 Mar 13;16(1):9. doi: 10.1186/s11689-024-09525-0.
Alexander G P Glebov-McCloud  #  1 ,  Walter S Saide  #  1 ,  Marie E Gaine  2  3 ,  Stefan Strack  4  5
Affiliations
  • 1. Department of Neuroscience and Pharmacology, Bowen Science Building, University of Iowa, Carver College of Medicine, 51 Newton Road, Iowa City, IA, 52242, USA.
  • 2. Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy Building, College of Pharmacy, University of Iowa, 180 S. Grand Ave, Iowa City, IA, 52242, USA.
  • 3. Iowa Neuroscience Institute, Intellectual and Developmental Disabilities Research Center, Iowa City, IA, USA.
  • 4. Department of Neuroscience and Pharmacology, Bowen Science Building, University of Iowa, Carver College of Medicine, 51 Newton Road, Iowa City, IA, 52242, USA. [email protected].
  • 5. Iowa Neuroscience Institute, Intellectual and Developmental Disabilities Research Center, Iowa City, IA, USA. [email protected].
  • # Contributed equally.
PMID: 38481146 DOI: 10.1186/s11689-024-09525-0
Abstract

Cyclic adenosine 3', 5' monophosphate (cAMP)-dependent Protein Kinase A (PKA) is a multi-functional serine/threonine kinase that regulates a wide variety of physiological processes including gene transcription, metabolism, and synaptic plasticity. Genomic Sequencing studies have identified both germline and somatic variants of the catalytic and regulatory subunits of PKA in patients with metabolic and neurodevelopmental disorders. In this review we discuss the classical cAMP/PKA signaling pathway and the disease phenotypes that result from PKA variants. This review highlights distinct isoform-specific cognitive deficits that occur in both PKA catalytic and regulatory subunits, and how tissue-specific distribution of these isoforms may contribute to neurodevelopmental disorders in comparison to more generalized endocrine dysfunction.

Keywords
CREB; Cognition; Endocrine Systems; Gene transcription; Kinases; Learning; MAPK; Memory; Metabolic Disorders; Movement Disorders; Neurodegeneration; Neurodevelopment; PKA; Protein phosphorylation; cAMP.