Sortilin, a novel APOE receptor implicated in Alzheimer disease

Carlo, Anne-Sophie

doi:10.4161/pri.26746

Cited by 31 publications

(28 citation statements)

References 30 publications

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“…It is worth noting that sortilin contains several hydrophobic stretches ( Supplementary Figure 4 ), which may serve as docking sites where low density lipoprotein can unload essential lipids such as dehydroepiandrosterone, ω-3 and, ω-6 fatty acids and cholesterol onto the lipid rafts of target cells [ 29 , 30 ]. A membrane invagination could then be activated to initiate endocytosis upon the binding of secreted gelsolin to sortilin.…”

Section: Discussionmentioning

confidence: 99%

Secreted gelsolin desensitizes and induces apoptosis of infiltrated lymphocytes in prostate cancer

et al. 2017

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Loss of immunosurveillance is a major cause of cancer progression. Here, we demonstrate that gelsolin, a constituent of ejaculate, induces apoptosis of activated lymphocytes in prostate cancer. Gelsolin was highly expressed in prostate cancer cells, and was associated with tumor progression, recurrence, metastasis, and poor prognosis. In vitro, secreted gelsolin inactivated CD4+ T cells by binding to CD37, and induced apoptosis of activated CD8+ T lymphocytes by binding to Fas ligand during cell contact dependent on major histocompatibility complex I. Moreover, secreted gelsolin bound to sortilin, which in turn bound to Wiskott-Aldrich syndrome protein family member 3, thereby enhancing the endocytosis and intracellular transport of essential lipids needed to facilitate tumor growth and expansion. Under normal conditions, gelsolin is a seemingly harmless protein that prevents immune responses in female recipients. In disease states, however, this protein can inhibit immunosurveillance and promote cancer progression.

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Section: Discussionmentioning

confidence: 99%

Secreted gelsolin desensitizes and induces apoptosis of infiltrated lymphocytes in prostate cancer

et al. 2017

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“…In the case of inhibited signaling pathways (Table 1 ), only SORT1 and PPP2CA were identified to be commonly present in multiple brain regions. SORT1 was present in the middle temporal gyrus and primary visual cortex, and this molecule has recently been found to act as a novel receptor for apolipoprotein E (APOE) (Carlo, 2013 ; Carlo et al, 2013 ). Importantly, ablation of sortilin expression in mice results in accumulation of APOE and Aβ in the brain resulting in AD like physiology the mice (Carlo, 2013 ).…”

Section: Resultsmentioning

confidence: 99%

Integrative Computational Network Analysis Reveals Site-Specific Mediators of Inflammation in Alzheimer's Disease

2018

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Alzheimer's disease (AD) is a major neurodegenerative disease and is one of the most common cause of dementia in older adults. Among several factors, neuroinflammation is known to play a critical role in the pathogenesis of chronic neurodegenerative diseases. In particular, studies of brains affected by AD show a clear involvement of several inflammatory pathways. Furthermore, depending on the brain regions affected by the disease, the nature and the effect of inflammation can vary. Here, in order to shed more light on distinct and common features of inflammation in different brain regions affected by AD, we employed a computational approach to analyze gene expression data of six site-specific neuronal populations from AD patients. Our network based computational approach is driven by the concept that a sustained inflammatory environment could result in neurotoxicity leading to the disease. Thus, our method aims to infer intracellular signaling pathways/networks that are likely to be constantly activated or inhibited due to persistent inflammatory conditions. The computational analysis identified several inflammatory mediators, such as tumor necrosis factor alpha (TNF-a)-associated pathway, as key upstream receptors/ligands that are likely to transmit sustained inflammatory signals. Further, the analysis revealed that several inflammatory mediators were mainly region specific with few commonalities across different brain regions. Taken together, our results show that our integrative approach aids identification of inflammation-related signaling pathways that could be responsible for the onset or the progression of AD and can be applied to study other neurodegenerative diseases. Furthermore, such computational approaches can enable the translation of clinical omics data toward the development of novel therapeutic strategies for neurodegenerative diseases.

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“…Previously, sortilin was known as the neurotensin receptor 3 [523]. Sortilin binds to and promotes ␣-cleavage of A␤PP and is responsible for ApoE-mediated cellular uptake and degradation of extracellular A␤ [524][525][526]. Significantly increased levels of sortilin were found in human AD brains and in 6-month old Swedish-A␤PP/PS1dE9 transgenic mice [527].…”

Section: Sortilin Receptor Inhibitorsmentioning

confidence: 99%

Cognitive Enhancers (Nootropics). Part 1: Drugs Interacting with Receptors

Froestl

Muhs

Pfeifer

2012

JAD

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Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 18 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease-modifying drugs meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs, whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. The review covers the evolution of research in this field over the last 25 years.

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Sortilin, a novel APOE receptor implicated in Alzheimer disease

Cited by 31 publications

References 30 publications

Secreted gelsolin desensitizes and induces apoptosis of infiltrated lymphocytes in prostate cancer

Secreted gelsolin desensitizes and induces apoptosis of infiltrated lymphocytes in prostate cancer

Integrative Computational Network Analysis Reveals Site-Specific Mediators of Inflammation in Alzheimer's Disease

Cognitive Enhancers (Nootropics). Part 1: Drugs Interacting with Receptors

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