Ask about this productRelated genes to: SORL1 antibody
- Gene:
- SORL1 NIH gene
- Name:
- sortilin related receptor 1
- Previous symbol:
- C11orf32
- Synonyms:
- gp250, LR11, LRP9, SorLA, SorLA-1
- Chromosome:
- 11q24.1
- Locus Type:
- gene with protein product
- Date approved:
- 1996-12-27
- Date modifiied:
- 2016-10-05
Related products to: SORL1 antibody
Related articles to: SORL1 antibody
- Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by profound molecular heterogeneity and high relapse rates, posing significant clinical challenges. Programmed cell death (PCD), encompassing diverse regulated modalities such as apoptosis, necroptosis, and ferroptosis, plays a key role in leukemogenesis and therapeutic response; however, a comprehensive prognostic framework integrating multi-modal PCD pathways in AML remains elusive. In this study, we performed a systematic transcriptomic analysis of 1624 genes associated with 13 distinct PCD forms. A novel computational pipeline combining a variational autoencoder (VAE) for dimensionality reduction and a multilayer perceptron (MLP) for classification was employed to identify robust PCD-related biomarkers, interpreted via SHapley Additive exPlanations (SHAP) analysis. This approach identified 48 candidate genes with discriminative potential between AML and normal bone marrow. Unsupervised consensus clustering based on these genes delineated two molecular subtypes exhibiting divergent clinical outcomes and immune microenvironment profiles. The subtype demonstrated an immunosuppressive phenotype, characterized by enriched regulatory T cells, M2 macrophages, and elevated expression of inhibitory immune checkpoints, correlating with inferior survival. We developed an 8-gene prognostic signature (, , , , , , and ) that effectively categorized patients into high- and low-risk groups with notable survival differences, validated across independent cohorts. A prognostic nomogram combining the risk score, age, and cytogenetic risk enhanced the prediction accuracy for overall survival. Our study presents an integrative model that connects multi-modal PCD pathways to AML prognosis, offering a new molecular subtyping system and a clinically applicable risk assessment tool for improved prognostication and personalized treatment strategies. - Source: PubMed
Publication date: 2026/03/27
Zhang ChunlongNi HaisenZhao ZiyiZhao Ning - The rs11218343 is a non-coding variant of genome-wide significance for sporadic Alzheimer's disease (AD) with one of the most protective effects known to date. It localizes to SORL1, encoding the AD risk factor Sortilin-related receptor with A type repeats (SORLA). Still, the functional significance of rs11218343 for AD-related processes remains unclear. - Source: PubMed
Gorniak-Walas MalgorzataTelugu Narasimha SRudolph Ina-MariaDiecke SebastianWillnow Thomas E - BackgroundAlzheimer's disease (AD) is a multifactorial disorder. The sortilin-related receptor 1 () gene, which regulates the trafficking and recycling of amyloid precursor protein, has been reported to be associated with the development of AD.ObjectiveThis study investigated the impact of polymorphisms (rs641120 and rs1784933) and their interaction with the apolipoprotein E () ε4 allele on AD preclinical stages-subjective cognitive decline (SCD) and mild cognitive impairment (MCI). We also explored the association between the rs641120 and serum biomarkers.MethodsThe study included 225 SCD, 131 MCI, and 62 normal controls (NC). Logistic regression models were utilized to assess genetic risks and interactions. Nonparametric tests or t-tests were employed to examine group differences stratified by protective genes in neuropsychological performance and biomarkers.ResultsThe rs641120 A allele was associated with a lower risk of SCD and MCI, within AA genotype (OR = 0.575) and AG genotype (OR = 0.588). In MCI patients, the A allele was associated with lower levels of serum Aβ and p-tau181. An interaction between rs1784933 and the ε4 allele was identified. In NC carrying ε4, AA is associated with higher risk of SCD (OR = 12.030, = 0.029) and MCI (OR = 10.015, = 0.044). In SCD patients without ε4, AA genotype is associated with lower risk of MCI (OR = 0.301, = 0.006).Conclusions polymorphisms influence SCD and MCI susceptibility and correlate with AD serum biomarkers. Additionally, we detected an interaction between rs1784933 and the ε4 genotype. - Source: PubMed
Publication date: 2026/04/17
Meng FanfanZhao TingtingYang XiLi HanboWang JiapingZhu QingyunLiu JinWang TongZhu Yi - Microglial dysfunction is a hallmark of Alzheimer's disease (AD), yet the molecular mechanisms driving these impairments remain poorly defined. Genetic studies implicate several AD-associated genes in regulating microglial activity, including SORL1, which encodes the sorting receptor SorLA. Although SorLA is highly expressed in microglia, its functional role in cellular homeostasis has remained unclear. Here, we investigated SorLA function using human brain tissue, primary microglia from rapid autopsies, and CRISPR-engineered human iPSC-derived microglia and neurons. Integrated multi-omics analyses, including single-cell RNA sequencing, lipidomics, and proteomics, together with biochemical and functional assays, revealed that SorLA deficiency induces endoplasmic reticulum (ER) stress and interferon signaling, promotes lipid droplet accumulation, and impairs phagocytic and immune functions. Protein co-complex mapping and structural modeling identified ER-associated proteins co-enriched with SorLA, including SUN2, calnexin (CANX), and multiple COPI complex components (COPA, COPB1, COPG1, ARCN1), implicating SorLA in ER proteostasis and intracellular trafficking. Notably, SORL1 deletion in iPSC-derived neurons recapitulated key phenotypes observed in microglia, including lipid droplet accumulation and SorLA-SUN2 co-immunoprecipitation, indicating that this ER-associated pathway operates across distinct brain cell types. Together, these findings identify an ER-related role for SorLA that extends beyond its established function in endocytic trafficking. Loss of SorLA triggers maladaptive stress responses, perturbs lipid handling, and compromises cellular resilience, thereby contributing to AD-relevant cellular dysfunction. - Source: PubMed
Publication date: 2026/04/06
Haq ImdadulNgo Jason CRoy NainikaLee EmilyChoudhury Muniyat ASoni Rajesh KTeich Andrew FMayeux Richard PDe Jager Philip LHe YeWu XuebingBennett David AOlah MartaSher Falak - Obesity and Alzheimer’s disease (AD) are epidemiologically associated. The locus coeruleus (LC)—the brain’s primary and most significant source of norepinephrine—is one of the earliest sites of neurodegeneration in AD. The LC participates in feeding behavior through connections with the hypothalamus. The cellular composition of the LC has been characterized at single-cell resolution. However, the constituent cellular signatures of genes related to energy homeostasis—such as the melanocortin pathway genes—in the LC are unclear. We performed single-nucleus RNA sequencing and spatial transcriptomics (Visium) in the human LC, and HiPlex RNAscope in the LC of mice. The melanocortin pathway gene was expressed in the majority of DBH neurons across the LC. was also co-expressed with AD-associated genes such as , , , and . More than 20% of Dbh neurons in the LC were positive for , , , and . is expressed in the central nervous system and modulates the trafficking and signaling of all five G-protein coupled receptors (GPCRs) of the melanocortin receptor family: Mc1r, Mc2r, Mc3r, Mc4r, and Mc5r. In mice, among the melanocortin receptors, showed the highest co-expression with , accounting for 17.9% of -positive cells, followed by with 10.9% of -positive cells. , , and showed very limited co-expression with . Our study reveals that many -positive cells do not express any melanocortin receptor genes, warranting future studies into metabolically relevant GPCRs downstream of MRAP2 in the LC. In summary, our study characterizes melanocortin molecular substrates in the human and mouse LC and highlights as a potential link between pathways of energy homeostasis and neurodegeneration. - Source: PubMed
Publication date: 2026/04/04
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