Uncovering the Significance of STEP61 in Alzheimer's Disease: Structure, Substrates, and Interactome

Cell Mol Neurobiol. 2023 Oct;43(7):3099-3113. doi: 10.1007/s10571-023-01364-2. Epub 2023 May 23.

Abstract

STEP (STriatal-Enriched Protein Tyrosine Phosphatase) is a brain-specific phosphatase that plays an important role in controlling signaling molecules involved in neuronal activity and synaptic development. The striatum is the main location of the STEP enzyme. An imbalance in STEP61 activity is a risk factor for Alzheimer's disease (AD). It can contribute to the development of numerous neuropsychiatric diseases, including Parkinson's disease (PD), schizophrenia, fragile X syndrome (FXS), Huntington's disease (HD), alcoholism, cerebral ischemia, and stress-related diseases. The molecular structure, chemistry, and molecular mechanisms associated with STEP61's two major substrates, Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAr) and N-methyl-D-aspartate receptors (NMDARs), are crucial in understanding the relationship between STEP61 and associated illnesses. STEP's interactions with its substrate proteins can alter the pathways of long-term potentiation and long-term depression. Therefore, understanding the role of STEP61 in neurological illnesses, particularly Alzheimer's disease-associated dementia, can provide valuable insights for possible therapeutic interventions. This review provides valuable insights into the molecular structure, chemistry, and molecular mechanisms associated with STEP61. This brain-specific phosphatase controls signaling molecules involved in neuronal activity and synaptic development. This review can aid researchers in gaining deep insights into the complex functions of STEP61.

Keywords: Alzheimer’s disease; Dementia; Glutamate receptors; Interactome; STEP61 enzyme.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease*
  • Humans
  • Long-Term Potentiation
  • Neuronal Plasticity
  • Phosphoric Monoester Hydrolases / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction / physiology

Substances

  • Phosphoric Monoester Hydrolases
  • Receptors, N-Methyl-D-Aspartate