.infobox .infobox-gene
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.infobox .infobox-gene th [10]
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CD38 is a transmembrane glycoprotein that functions as both an ecto-enzyme and a receptor. It catalyzes the synthesis and hydrolysis of cyclic ADP-ribose (cADPR), a key calcium-mobilizing second messenger. CD38 is expressed in various tissues including brain cells (neurons, astrocytes, microglia) and plays important roles in neuroinflammation, synaptic plasticity, and neurodegeneration[11].
CD38 (gene symbol: CD38) is a type II transmembrane protein originally identified as a surface marker on hematopoietic cells. In the brain, CD38 is expressed in neurons and glial cells, where it regulates intracellular calcium levels through its enzymatic activity[12].
The CD38 gene (Gene ID: 933) is located on chromosome 4p15.32 and encodes a protein of 301 amino acids. The CD38 protein structure consists of:
CD38 exists as a homodimer on the cell surface and undergoes conformational changes upon ligand binding[13].
CD38 is the primary enzyme responsible for synthesizing cADPR from NAD⁺ in mammalian cells. cADPR acts as a potent second messenger that releases calcium from intracellular stores (endoplasmic reticulum) through ryanodine receptors[14].
CD38 contributes to cellular NAD⁺ consumption and regulates NAD⁺/NADH ratios, affecting metabolic processes and sirtuin activity[1:1].
In immune cells, CD38 regulates cytokine production, phagocytosis, and cell proliferation through calcium-dependent signaling[2:1].
CD38 plays complex roles in AD pathogenesis:
CD38 is upregulated in AD brain tissue and promotes inflammatory responses in microglia through enhanced calcium signaling and cytokine production[3:1].
AD brains show reduced NAD⁺ levels, partially due to CD38 overexpression. This affects sirtuin activity (particularly SIRT1) and mitochondrial function[4:1].
CD38 deficiency in APP/PS1 mice reduces amyloid plaque load and improves cognitive function, suggesting pathogenic role of CD38 in AD[5:1].
CD38 regulates neuroinflammatory responses through multiple mechanisms:
CD38 expression increases in activated microglia, driving production of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6)[7:1].
CD38 in astrocytes mediates calcium waves and ATP release, affecting neuroinflammatory cascades[8:1].
CD38 on CNS-infiltrating T cells modulates neuroinflammatory responses in autoimmune and degenerative conditions[9:1].
CD38 is upregulated in HIV-infected macrophages and microglia, contributing to chronic neuroinflammation and neuronal dysfunction in HAND patients[10:1].
CD38 interacts with multiple proteins and pathways:
The study of Cd38 Molecule (Cd38) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Ruggieri A, et al. (2015) CD38 in neuroinflammation. Adv Exp Med Biol. 2015. ↩︎ ↩︎
Blacher E, et al. (2015) Alzheimer disease pathology as a host response. Nat Neurosci. 2015. ↩︎ ↩︎
Roboon J, et al. (2019) CD38 in neurodegenerative diseases. J Neurochem. 2019. ↩︎ ↩︎
Hattori T, et al. (2016) CD38 and its role in the brain. Adv Exp Med Biol. 2016. ↩︎ ↩︎
Garlisi CG, et al. (2003) CD38 as a therapeutic target. Mol Med. 2003. ↩︎ ↩︎
Lund FE, et al. (2019) CD38 and calcium signaling in immune cells. Curr Opin Immunol. 2019. ↩︎ ↩︎
Zocchi E, et al. (2019) CD38 in age-related neurodegeneration. Aging Cell. 2019. ↩︎ ↩︎
Chiollaz M, et al. (2020) CD38 in Alzheimer's disease. J Alzheimers Dis. 2020. ↩︎ ↩︎
Piedrahita D, et al. (2016) CD38 on hippocampal neurons. J Neurochem. 2016. ↩︎ ↩︎
Cao W, et al. (2018) HIV-associated neurocognitive disorder and CD38. J Neurovirol. 2018. ↩︎ ↩︎
Malavasi F, et al. (2008) CD38: a target for immunotherapeutic approaches. Nat Rev Cancer. 2008. ↩︎
Quarona V, et al. (2013) Unraveling the contribution of CD38 to neurodegeneration. Exp Neurol. 2013. ↩︎
Lee HC, et al. (2014) CD38 and CD157 as therapeutic targets. Mol Med. 2014. ↩︎
Guse AH. (2005) Second messenger function and the structure of cADPR. Cell Calcium. 2005. ↩︎