The Interaction Between Contactin and Amyloid Precursor Protein and Its Role in Alzheimer’s Disease

Bamford, Rosemary A.; Widagdo, Jocelyn; Takamura, Natsuki; Eve, Madeline; Anggono, Victor; Oguro-Ando, Asami

doi:10.1016/j.neuroscience.2019.10.006

Cited by 30 publications

(23 citation statements)

References 214 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Noteworthy that CNTN2 showed association at both SNP and gene‐level analysis in the present study. Protein encoded by CNTN2 interacts with proteins involved in Alzheimer's Disease (AD) pathogenesis (APP and BACE1) (Bamford et al, 2020), a disease recently linked to Porphyromonas gingivalis (Dominy et al, 2019). Furthermore, the second most upregulated gene in the current study was RSPO4 .…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide association study of stage III/IV grade C periodontitis (former aggressive periodontitis) in a Spanish population

Coo

Cruz

Quintela

et al. 2021

J Clinic Periodontology

View full text Add to dashboard Cite

Aim To identify loci associated with stages III/IV, grade C periodontitis (PIII/IV‐C) through a genome‐wide association study (GWAS). Materials and Methods 441 Caucasian Spanish PIII/IV‐C cases from the SEPA Network of Research Clinics and 1141 controls from the Banco Nacional de ADN were genotyped with “Axiom Spain Biobank Array,” which contains 757836 markers, including rare and low‐frequency Spanish variants. The analysis of the individual association and subsequently the gene‐level analysis with Sequence Kernel Association Test (SKAT) were carried out adjusting for age, sex and PC1 covariates. Pathway Analysis was additionally performed with Ingenuity Pathway Analysis (IPA) software on the top associated genes. Results In the individual analyses, no genome‐wide significant signals were detected. However, 8 SNPs of 8 loci reached suggestive evidence of association with PIII/IV‐C, including FAT3 rs35709256, CSNK1G2 rs4807188, MYH13 rs2074872, CNTN2 rs116611488, ANTXR1 rs4854545, 8p23.2 rs78672540, ANGPT1 rs13439823 and PLEC rs11993287 (p < 5 × 10−6). SKAT analysis identified other interesting signals at CNTN2, FBXO44, AP1M2, RSPO4, KRI1, BPIFB1 and INMT, although their probability does not exceed the multiple‐test correction. IPA indicated significant enrichment of pathways related to cAMP, IL‐2, CD28, VDR/RXR and PI3K/Akt. Conclusions GWAS found no SNPs significantly associated with PIII/IV‐C.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome‐wide association study of stage III/IV grade C periodontitis (former aggressive periodontitis) in a Spanish population

Coo

Cruz

Quintela

et al. 2021

J Clinic Periodontology

View full text Add to dashboard Cite

show abstract

“…The levels of contactin-2 also decrease with age in mice ( Tachi et al, 2010 ). The chromosomal region encompassing the contactin-4 coding gene was found to have suggestive linkage to late-onset AD ( Blacker et al, 2003 ; Bamford et al, 2020 ).…”

Section: Interactions Of Cams With App and The Role That Cams Play In...mentioning

confidence: 99%

Amyloid precursor protein (APP) and amyloid β (Aβ) interact with cell adhesion molecules: Implications in Alzheimer’s disease and normal physiology

Pfundstein

Nikonenko

Sytnyk

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is an incurable neurodegenerative disorder in which dysfunction and loss of synapses and neurons lead to cognitive impairment and death. Accumulation and aggregation of neurotoxic amyloid-β (Aβ) peptides generated via amyloidogenic processing of amyloid precursor protein (APP) is considered to play a central role in the disease etiology. APP interacts with cell adhesion molecules, which influence the normal physiological functions of APP, its amyloidogenic and non-amyloidogenic processing, and formation of Aβ aggregates. These cell surface glycoproteins also mediate attachment of Aβ to the neuronal cell surface and induce intracellular signaling contributing to Aβ toxicity. In this review, we discuss the current knowledge surrounding the interactions of cell adhesion molecules with APP and Aβ and analyze the evidence of the critical role these proteins play in regulating the processing and physiological function of APP as well as Aβ toxicity. This is a necessary piece of the complex AD puzzle, which we should understand in order to develop safe and effective therapeutic interventions for AD.

show abstract

“…The CNTN4-APP interaction has been observed in the olfactory bulb and retinal axons of the retinotectal system, which are regions where the development of axon-axon and axon-target contacts is crucial (Osterhout et al, 2015). Alterations in CNTN4 expression have been implicated to negatively affect the proteolytic processing of APP, which contributes to impairments in axon guidance and synaptic plasticity, reduced neuronal survival, and ultimately results in cognitive impairments (Bamford et al, 2020). Finally, deficiencies in CHL1, CNTN6, and CNTN4 may impair the formation and stabilization of synapses due to their role as synaptic adhesion molecules.…”

Section: Future Directionsmentioning

confidence: 99%

Cell Adhesion Molecules Involved in Neurodevelopmental Pathways Implicated in 3p-Deletion Syndrome and Autism Spectrum Disorder

Gandawijaya

Bamford

Burbach

et al. 2021

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is characterized by impaired social interaction, language delay and repetitive or restrictive behaviors. With increasing prevalence, ASD is currently estimated to affect 0.5–2.0% of the global population. However, its etiology remains unclear due to high genetic and phenotypic heterogeneity. Copy number variations (CNVs) are implicated in several forms of syndromic ASD and have been demonstrated to contribute toward ASD development by altering gene dosage and expression. Increasing evidence points toward the p-arm of chromosome 3 (chromosome 3p) as an ASD risk locus. Deletions occurring at chromosome 3p result in 3p-deletion syndrome (Del3p), a rare genetic disorder characterized by developmental delay, intellectual disability, facial dysmorphisms and often, ASD or ASD-associated behaviors. Therefore, we hypothesize that overlapping molecular mechanisms underlie the pathogenesis of Del3p and ASD. To investigate which genes encoded in chromosome 3p could contribute toward Del3p and ASD, we performed a comprehensive literature review and collated reports investigating the phenotypes of individuals with chromosome 3p CNVs. We observe that high frequencies of CNVs occur in the 3p26.3 region, the terminal cytoband of chromosome 3p. This suggests that CNVs disrupting genes encoded within the 3p26.3 region are likely to contribute toward the neurodevelopmental phenotypes observed in individuals affected by Del3p. The 3p26.3 region contains three consecutive genes encoding closely related neuronal immunoglobulin cell adhesion molecules (IgCAMs): Close Homolog of L1 (CHL1), Contactin-6 (CNTN6), and Contactin-4 (CNTN4). CNVs disrupting these neuronal IgCAMs may contribute toward ASD phenotypes as they have been associated with key roles in neurodevelopment. CHL1, CNTN6, and CNTN4 have been observed to promote neurogenesis and neuronal survival, and regulate neuritogenesis and synaptic function. Furthermore, there is evidence that these neuronal IgCAMs possess overlapping interactomes and participate in common signaling pathways regulating axon guidance. Notably, mouse models deficient for these neuronal IgCAMs do not display strong deficits in axonal migration or behavioral phenotypes, which is in contrast to the pronounced defects in neuritogenesis and axon guidance observed in vitro. This suggests that when CHL1, CNTN6, or CNTN4 function is disrupted by CNVs, other neuronal IgCAMs may suppress behavioral phenotypes by compensating for the loss of function.

show abstract

The Interaction Between Contactin and Amyloid Precursor Protein and Its Role in Alzheimer’s Disease

Cited by 30 publications

References 214 publications

Genome‐wide association study of stage III/IV grade C periodontitis (former aggressive periodontitis) in a Spanish population

Genome‐wide association study of stage III/IV grade C periodontitis (former aggressive periodontitis) in a Spanish population

Amyloid precursor protein (APP) and amyloid β (Aβ) interact with cell adhesion molecules: Implications in Alzheimer’s disease and normal physiology

Cell Adhesion Molecules Involved in Neurodevelopmental Pathways Implicated in 3p-Deletion Syndrome and Autism Spectrum Disorder

Contact Info

Product

Resources

About