Cyclic ADP-ribose

Cyclic ADP-ribose (cADPR) is a calcium-mobilizing nucleotide involved in the physiological regulation of intracellular calcium levels. cADPR acts as a second messenger in various cellular processes, including calcium signaling, cell proliferation, and cell differentiation. It is synthesized from NAD+ by the enzyme ADP-ribosyl cyclase and can be hydrolyzed back to ADP-ribose by CD38 and other enzymes.

Biosynthesis and Degradation

The biosynthesis of cADPR is catalyzed by ADP-ribosyl cyclase, which converts NAD+ into cADPR. This reaction is crucial for the regulation of intracellular calcium levels. The degradation of cADPR, on the other hand, is primarily facilitated by the enzyme CD38, which hydrolyzes cADPR to ADP-ribose, thereby terminating its action as a second messenger.

Function

cADPR plays a significant role in calcium signaling pathways. It functions by binding to and activating ryanodine receptors (RyRs) located on the endoplasmic reticulum (ER) membrane. This activation leads to the release of calcium ions from the ER into the cytoplasm, increasing intracellular calcium levels and triggering various cellular responses. cADPR-mediated calcium release is involved in processes such as muscle contraction, neurotransmitter release, and gene expression.

Calcium Signaling

In calcium signaling, cADPR acts as a key regulator by modulating the release of calcium from intracellular stores. This regulation is essential for the proper functioning of cells and the coordination of cellular activities.

Cell Proliferation and Differentiation

cADPR also plays a role in cell proliferation and differentiation. By influencing calcium levels within the cell, cADPR can affect the activation of transcription factors and other molecules involved in cell growth and development.

Clinical Significance

Alterations in cADPR levels and its signaling pathways have been implicated in various diseases, including heart disease, diabetes, and neurodegenerative diseases. Understanding the mechanisms of cADPR signaling could lead to new therapeutic targets for these conditions.

Research

Research on cADPR has focused on elucidating its role in calcium signaling and its implications for health and disease. Studies have explored the potential of targeting cADPR pathways for the treatment of diseases associated with dysregulated calcium signaling.

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