A Friend or Foe: Calcineurin across the Gamut of Neurological Disorders

Abstract

The serine/threonine phosphatase calcineurin (CaN) is a unique but confounding calcium/calmodulin-mediated enzyme. CaN has shown to play essential roles from regulating calcium homeostasis to being an intricate part of learning and memory formation. Neurological disorders, despite differing in their etiology, share similar pathological outcomes, such as mitochondrial dysfunction and apoptotic signaling brought about by excitotoxic elements. CaN, being deeply integrated in vital neuronal functions, may be implicated in various neurological disorders. Understanding the enzyme and its physiological niche in the nervous system is vital in uncovering its roles in the spectrum of brain disorders. By reviewing the crosstalk in different neurological pathologies, a possible grasp of CaN’s complex signaling may lead to forming better neurotherapy. This Outlook attempts to explore the various neuronal functions of CaN and investigate its pervasive role through the gamut of neurological disorders.

Endoplasmic reticulum–mitochondria crosstalk: from junction to function across neurological disorders

“…A). Despite well‐established pathogenicity, there is currently no treatment to control production and accumulation of the different Aβ peptides (typically Aβ40 and Aβ42), and several efforts have failed to combat the onset/progression of the pathology . This is consistent with the conclusion that additional molecular mechanisms besides accumulation of Aβ may be involved in AD pathology.…”

Calcineurin-Modulated Antimicrobial Peptide Expression Is Required for the Development of Helicoverpa armigera

“…HaCAN is a critical dephosphorylase and its ubiquitous expression in different instars and tissues indicates that HaCAN participates in many biological pathways (Figure 2). The importance of CAN has been reported in other species including mammals and Drosophila (Dijkers and O’Farrell, 2007; Jackson et al, 2018; Kweon et al, 2018). CAN shares a high amino acid identity cross different species, which indicates that CAN may have similar functions in these different species (Chen and Zhang, 2013; Zhao et al, 2018).…”

“…In addition, In human endothelial cells, CAN functions as a mediator of anaphylaxis (Ballesteros-Martinez et al, 2017). These studies provide key evidence that CAN is a vital signaling molecule that performs a variety of functions in different biological pathways (Liu et al, 1991; Jackson et al, 2018).…”

“…Studies have reported that CAN is predominantly expressed in the brain and plays important roles in various neuronal functions and disorders. This is due to CAN’s vital functions in Ca 2+ homeostasis, synaptic plasticity, receptor signaling, and transcription regulation (Jackson et al, 2018). Furthermore, CAN is also found to be expressed in lymphocytes and macrophages, in which CAN has been confirmed to be took part in innate immunity (Bueno et al, 2002; Kang et al, 2007).…”

The activity of the Striatal‐enriched protein tyrosine phosphatase in neuronal cells is modulated by adenosine A2A receptor

“…Furthermore, we could provide evidence of a critical role played by intracellular calcium and calcineurin in the A 2A R‐induced STEP activation. Calcineurin is a Ca 2+ /calmodulin‐dependent serine/threonine phosphatase ubiquitous in most mammalian tissues but predominating in the brain (Rusnak and Mertz ; Saraf et al ), which regulates STEP phosphorylation through a Ca 2+ ‐dependent mechanism (Paul et al ). We found that in the SH‐SY5Y neuroblastoma cell line, A 2A R stimulation with CGS 21680 induced a small but significant intracellular Ca 2+ increase that could be responsible for calcineurin recruitment and STEP activation.…”