Endolysosome and autophagy dysfunction in Alzheimer disease

Hung, Christy; Livesey, Frederick J.

doi:10.1080/15548627.2021.1963630

Cited by 24 publications

(5 citation statements)

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“…Abnormalities within the neurons in the lysosomal and autophagy/macroautophagy systems are prominent features of the early stages of Alzheimer’s disease (AD). SORL1 mutations are an important cause of rare autosomal dominant AD, increasing the risk of late-onset AD ( 43 ). The deletion of SORL1 may affect the regulatory protein-induced cell proliferation enabling metastatic resistance to HER2 treatment in breast cancer cells ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Upregulated of ANXA3, SORL1, and Neutrophils May Be Key Factors in the Progressionof Ankylosing Spondylitis

Jiang

Zhan

et al. 2022

Front. Immunol.

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IntroductionThe specific pathogenesis of ankylosing spondylitis (AS) remains unclear, and our study aimed to investigate the possible pathogenesis of AS.Materials and MethodsTwo datasets were downloaded from the GEO database to perform differentially expressed gene analysis, GO enrichment analysis, KEGG pathway analysis, DO enrichment analysis, GSEA analysis of differentially expressed genes, and construction of diagnostic genes using SVM and WGCNA along with Hypoxia-related genes. Also, drug sensitivity analysis was performed on diagnostic genes. To identify the differentially expressed immune genes in the AS and control groups, we analyzed the composition of immune cells between them. Then, we examined differentially expressed genes in three AS interspinous ligament specimens and three Degenerative lumbar spine specimens using high-throughput sequencing while the immune cells were examined using the neutrophil count data from routine blood tests of 1770 HLA-B27-positive samples and 7939 HLA-B27-negative samples. To assess the relationship between ANXA3 and SORL1 and disease activity, we took the neutrophil counts of the first 50 patients with above-average BASDAI scores and the last 50 patients with below-average BASDAI scores for statistical analysis. We used immunohistochemistry to verify the expression of ANXA3 and SORL1 in AS and in controls.ResultsANXA3 and SORL1 were identified as new diagnostic genes for AS. These two genes showed a significant differential expression between AS and controls, along with showing a significant positive correlation with the neutrophil count. The results of high-throughput sequencing verified that these two gene deletions were indeed differentially expressed in AS versus controls. Data from a total of 9707 routine blood tests showed that the neutrophil count was significantly higher in AS patients than in controls (p < 0.001). Patients with AS with a high BASDAI score had a much higher neutrophil count than those with a low score, and the difference was statistically significant (p < 0.001). The results of immunohistochemistry showed that the expression of ANXA3 and SORL1 in AS was significantly higher than that in the control group.ConclusionUpregulated of ANXA3, SORL1, and neutrophils may be a key factor in the progression of Ankylosing spondylitis.

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Section: Discussionmentioning

confidence: 99%

Upregulated of ANXA3, SORL1, and Neutrophils May Be Key Factors in the Progressionof Ankylosing Spondylitis

Jiang

Zhan

et al. 2022

Front. Immunol.

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“…Research on AD encompasses various aspects such as immune regulation 39 , autophagy 40,41 , mitochondrial function 42 , and more. The AD-related pathways identified across 14 brain regions span multiple domains, highlighting their significance.…”

Section: Discussionmentioning

confidence: 99%

Identifying Alzheimer’s disease-related pathways based on whole-genome sequencing data

Wang,

Liu,

et al. 2024

Preprint

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Alzheimer’s disease (AD) is a highly inheritable neurodegenerative disorder for which pathway-specific genetic profiling provides insights into its key biological mechanisms and potential treatment targets. Traditional disease-pathway analyses for AD have certain limitations, such as environmental interference and arbitrary sample division. We present a comprehensive framework that starts with genome data, avoiding these drawbacks and offering intrinsic pathway-specific genetic profiling for AD. Whole genome sequencing data from 173 individuals were used to quantify transcriptomes in 14 brain regions, estimate individual-level pathway variant scores, and analyze AD risk for each patient. These results were combined to identify AD-related pathways and quantify their interactions. The predicted expression levels were consistent with previous findings, and the estimated AD risk showed a significant correlation with Braak/Thal scores. A total of 3,798 pathways were identified as potentially associated with AD, with about 19.7% previously reported. Key pathways, including NF-κB signaling and GSK3β activation, were linked to AD pathogenesis. The interactions among pathways highlighted shared gene functions in AD. In summary, we provided an effective framework for disease-pathway analysis, revealing the interdependence or compensatory effects of pathways in AD.

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“…Biomarker measurements could be used as patient inclusion criteria to monitor disease progression and assess the treatment's efficacy. In addition, the endo-lysosomal pathway is often highly interconnected with other processes and organelles like autophagy [ 107 , 108 ] and mitochondria [ 66 , 67 ]. Therefore, centring future research on these intracellular interactions may uncover novel biomarkers that are not necessarily derived from exosomes.…”

Section: Disruption Of the Endo-lysosomal System In Neurodegenerative...mentioning

confidence: 99%

Endo-lysosomal dysfunction in neurodegenerative diseases: opinion on current progress and future direction in the use of exosomes as biomarkers

Herman,

Randall,

Spiegel

et al. 2024

Phil. Trans. R. Soc. B

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Over the past two decades, increased research has highlighted the connection between endosomal trafficking defects and neurodegeneration. The endo-lysosomal network is an important, complex cellular system specialized in the transport of proteins, lipids, and other metabolites, essential for cell homeostasis. Disruption of this pathway is linked to a wide range of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and frontotemporal dementia. Furthermore, there is strong evidence that defects in this pathway create opportunities for diagnostic and therapeutic intervention. In this Opinion piece, we concisely address the role of endo-lysosomal dysfunction in five neurodegenerative diseases and discuss how future research can investigate this intracellular pathway, including extracellular vesicles with a specific focus on exosomes for the identification of novel disease biomarkers. This article is part of a discussion meeting issue ‘Understanding the endo-lysosomal network in neurodegeneration’.

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Endolysosome and autophagy dysfunction in Alzheimer disease

Cited by 24 publications

References 1 publication

Upregulated of ANXA3, SORL1, and Neutrophils May Be Key Factors in the Progressionof Ankylosing Spondylitis

Upregulated of ANXA3, SORL1, and Neutrophils May Be Key Factors in the Progressionof Ankylosing Spondylitis

Identifying Alzheimer’s disease-related pathways based on whole-genome sequencing data

Endo-lysosomal dysfunction in neurodegenerative diseases: opinion on current progress and future direction in the use of exosomes as biomarkers

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