β-Amyloid precursor protein (βAPP) in human gut with special reference to the enteric nervous system

Cabal, Álvaro Arias; Alonso-Cortina, V.; Gonzalez-Vazquez, L.O.; Naves, F.J.; Soto, Miguel; Vega, J.A.

doi:10.1016/0361-9230(95)02006-d

Cited by 18 publications

(8 citation statements)

References 22 publications

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“…Although there is one report of human APP protein localization in endothelial cells of the gut (Cabal et al, 1995), there are no reports in the literature of APP mRNA expression in vascular cells. A previous study showed that appa gene expression is first detectable at the mid-gastrula stage in the zebrafish embryo (Musa et al, 2001).…”

Section: Resultsmentioning

confidence: 99%

Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins

Liao

Wang

Watt

et al. 2012

Developmental Dynamics

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Background The single spanning transmembrane amyloid precursor protein (APP) and its proteolytic product, amyloid-beta (Aβ) peptide, have been intensely studied due to their role in the pathogenesis of Alzheimer’s disease. However, the biological role of the secreted ectodomain of APP, which is also generated by proteolytic cleavage, is less well understood. Here, we report Tol2 red fluorescent protein (RFP) transposon gene trap integrations in the zebrafish amyloid precursor protein a (appa) and amyloid precursor-like protein 2 (aplp2) genes. The transposon integrations are predicted to disrupt the appa and aplp2 genes to primarily produce secreted ectodomains of the corresponding proteins that are fused to RFP. Results Our results indicate the Appa-RFP and Aplp2 fusion proteins are likely secreted from the central nervous system and accumulate in the embryonic veins independent of blood flow. Conclusions The zebrafish appa and aplp2 transposon insertion alleles will be useful for investigating the biological role of the secreted form of APP.

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Section: Resultsmentioning

confidence: 99%

Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins

Liao

Wang

Watt

et al. 2012

Developmental Dynamics

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“…Patients with AD exhibit diverse CNS and ENS dysfunctions (Table 1). Since ENS neurons, the majority of which are cholinergic, also express APP (111,112), it would be reasonable to expect that the ENS would mirror the CNS in losing cholinergic neurons. However, pathological examination of the ENS in patients with AD showed no disease-associated neurodegeneration (113), suggesting that adult neurogenic programs may be responsible for sustaining ENS structure (34).…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Neurodegenerative disorders and gut-brain interactions

Singh¹,

Dawson²,

Kulkarni³

2021

Journal of Clinical Investigation

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Neurodegenerative disorders (NDs) are chronic and progressive disorders that disproportionately affect the elderly and have been characterized by selective loss of neurons in the CNS (1). Their prevalence is increasing -partly owing to extensions in lifespan -and by 2030, individuals affected by NDs will account for more than 8 million patients in the United States (2). Various NDs can be characterized and differentiated by their primary clinical features, the anatomical location of the neurodegeneration, the various cell types they affect, and/or the principal molecular abnormality that causes them (3).Prior to the considerable progress made in recent years that will be discussed here, psychiatrists, neurologists, and gastroenterologists alike supported the idea of the existence of a disease called the "institutional colon." This term described the presence of an amotile and/or elongated and largely distended colon with resulting gut dysfunctions in psychiatric patients who lived in mental health institutions (4). That such a disease existed was often questioned by contemporary physicians, and the confluence of gut and behavioral dysfunction was ascribed to the side effects of medicines, incorrect or inadequate diets, or inattention. To prove that the "institutional colon" is a true disease, Sonnenberg et al. (4) combed through millions of medical records at the US Veterans Affairs to show that patients with presenile dementia, Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), or Huntington's disease (HD) had significantly higher odds of also experiencing colonic dysfunction. The authors pointed out that "not all neurons involved in control of intestinal motility are located within the enteric nervous system, but may originate, for instance, in the vagal nuclei at the medulla oblongata or in the sacral segments of the spinal cord" and that "any referral to the loss of neuronal control of colonic motility does not allude to a common pathway, and leaves a multitude of heterogeneous mechanisms possible" (4). This landmark study showing the involvement of both gut and brain dysfunction in NDs paved the way for the studies discussed in this Review.Here, we review the processes associated with ND etiology and how various gut-innervating and gut-brain connecting neurons are either affected in NDs or are involved in their etiology. We also review the role of microbiota in driving NDs and discuss some open questions in this field. This Review will focus on the classical NDs -PD, AD, HD, and ALS -given that these are not only the major NDs but are also the diseases for which substantial information is available about associated gut dysfunctions.Neurodegenerative disorders (NDs) affect essential functions not only in the CNS, but also cause persistent gut dysfunctions, suggesting that they have an impact on both CNS and gut-innervating neurons. Although the CNS biology of NDs continues to be well studied, how gut-innervating neurons, including those that connect the gut to the brain, ...

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“…Aβ aggregation can start at a lower concentration, due to specific mutations within Aβ and its precursor that augment the propensity of Aβ peptides to aggregate, forming the basis for hereditary early-onset familial AD ( 22 ). Our group and others have already reviewed the literature on the possible sources of Aβ in AD and certain other diseases ( 16 , 46 , 94 ), and it has been suggested that there is significant local production of Aβ by neurons and probably astrocytes and that APP processing can be found in the brain and enteric nervous system ( 15 , 95 , 96 ). There is strong evidence that cultured neurons may produce Aβ and even form “plaques in the dish” ( 16 ).…”

Section: Aβ Is An Innate Immunity Weapon Released By Plateletsmentioning

confidence: 99%

On the Role of Platelet-Generated Amyloid Beta Peptides in Certain Amyloidosis Health Complications

et al. 2020

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As do many other immunity-related blood cells, platelets release antimicrobial peptides that kill bacteria, fungi, and even certain viruses. Here we review the literature suggesting that there is a similarity between the antimicrobials released by other blood cells and the amyloid-related Aβ peptide released by platelets. Analyzing the literature, we also propose that platelet-generated Aβ amyloidosis may be more common than currently recognized. This systemic Aβ from a platelet source may participate in various forms of amyloidosis in pathologies ranging from brain cancer, glaucoma, skin Aβ accumulation, and preeclampsia to Alzheimer’s disease and late-stage Parkinson’s disease. We also discuss the advantages and disadvantages of specific animal models for studying platelet-related Aβ. This field is undergoing rapid change, as it evaluates competing ideas in the light of new experimental observations. We summarized both in order to clarify the role of platelet-generated Aβ peptides in amyloidosis-related health disorders, which may be helpful to researchers interested in this growing area of investigation.

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β-Amyloid precursor protein (βAPP) in human gut with special reference to the enteric nervous system

Cited by 18 publications

References 22 publications

Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins

Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins

Neurodegenerative disorders and gut-brain interactions

On the Role of Platelet-Generated Amyloid Beta Peptides in Certain Amyloidosis Health Complications

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