Siglecs in Brain Function and Neurological Disorders

Abstract

Siglecs (Sialic acid-binding immunoglobulin-type lectins) are a I-type lectin that typically binds sialic acid. Siglecs are predominantly expressed in immune cells and generate activating or inhibitory signals. They are also shown to be expressed on the surface of cells in the nervous system and have been shown to play central roles in neuroinflammation. There has been a plethora of reviews outlining the studies pertaining to Siglecs in immune cells. However, this review aims to compile the articles on the role of Siglecs in brain function and neurological disorders. In humans, the most abundant Siglecs are CD33 (Siglec-3), Siglec-4 (myelin-associated glycoprotein/MAG), and Siglec-11, Whereas in mice the most abundant are Siglec-1 (sialoadhesin), Siglec-2 (CD22), Siglec-E, Siglec-F, and Siglec-H. This review is divided into three parts. Firstly, we discuss the general biological aspects of Siglecs that are expressed in nervous tissue. Secondly, we discuss about the role of Siglecs in brain function and molecular mechanism for their function. Finally, we collate the available information on Siglecs and neurological disorders. It is intriguing to study this family of proteins in neurological disorders because they carry immunoinhibitory and immunoactivating motifs that can be vital in neuroinflammation.

Neurology-related protein biomarkers are associated with cognitive ability and brain volume in older age

“…It was also associated with reactive astrogliosis in mice 27 and enriched in mouse astrocytes 28 , indicating that higher levels of this protein may reduce cognitive ability by reducing the number of healthy neurons. Other proteins that were relatively strongly associated with general fluid cognitive ability in the LBC1936 and the metaanalysis of the LBC1936 and INTERVAL-Old sample included sialoadhesin encoded by the SIGLEC1 gene on chromosome 20, a member of the immunoglobulin family 29 , which may influence cognitive ability through its roles in demyelination and neuroinflammation 30 ; poliovirus receptor encoded by the PVR gene on chromosome 19-viral infections have been previously linked to neurodegeneration 31 ; R-spondin-1 encoded by the RSPO1 gene on chromosome 1 and expressed in the central nervous system during development 32 ; discoidin domain receptor family, member 1 encoded by the DDR1 gene on chromosome 6, which is important in myelination 33 . The addition of smoking status and antihypertensive drug use as covariates slightly attenuated many of the results.…”

Dietary Flavonoids in p53—Mediated Immune Dysfunctions Linking to Cancer Prevention

“…One such protein family is Siglecs [86]. Siglecs are receptors that are expressed on the surface of white blood cells and bind to sialic acids (Sia), a nine carbon atom monosaccharide [86][87][88]. Most members of this family carry an inhibitory motif and lead to the suppression of immune response [86][87][88].…”

“…Siglecs are receptors that are expressed on the surface of white blood cells and bind to sialic acids (Sia), a nine carbon atom monosaccharide [86][87][88]. Most members of this family carry an inhibitory motif and lead to the suppression of immune response [86][87][88]. Siglecs have been implicated in immunological response in many physiological and pathological conditions, including cancer [89][90][91][92][93][94].…”

Sialic Acid-Siglec Axis as Molecular Checkpoints Targeting of Immune System: Smart Players in Pathology and Conventional Therapy

“…Changes in PSA-NCAM expression in response to stress stimuli may reflect hippocampus atrophy in long-term exposure to corticosteroids known as endocrine modulators in stress [59]. On the cellular level, the polysialylated NCAMs are recruited in neuron-microglia interaction via Siglec-11 binding and ITIM-coupled signaling, and they restrict damage by immune cells during brain inflammation [60,61]. This scenario could reflect immune controlling mechanisms in the brain after exposure to proinflammatory factors.…”