Prion Protein Signaling in the Nervous System—A Review and Perspective

Liebert, Ann; Bicknell, Brian; Adams, Roger

doi:10.4137/sti.s12319

Cited by 10 publications

(11 citation statements)

References 268 publications

(474 reference statements)

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“…Prion diseases, on the other hand, have spongiform vacuolation, gliosis, neuronal loss and deposition of amyloid molecules immune-positive for prion protein (PrP) as hallmarks of the disease [ 24 ]. Thus, prion disorders are caused by the misfolded form of the prion protein, denoted prion protein scrapie (PrP Sc ) [ 32 ]. The toxic misfolded PrP Sc has a high content of β-sheet in its secondary structure, which generates a highly hydrophobic and insoluble protein with a high tendency to aggregate and form amyloid structures [ 24 , 32 ].…”

Section: Protein Misfolding and Its Accumulation In Neurodegeneratmentioning

confidence: 99%

“…Thus, prion disorders are caused by the misfolded form of the prion protein, denoted prion protein scrapie (PrP Sc ) [ 32 ]. The toxic misfolded PrP Sc has a high content of β-sheet in its secondary structure, which generates a highly hydrophobic and insoluble protein with a high tendency to aggregate and form amyloid structures [ 24 , 32 ].…”

Section: Protein Misfolding and Its Accumulation In Neurodegeneratmentioning

confidence: 99%

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Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration

González-Sanmiguel

Schuh

Muñoz-Montesino

et al. 2020

Cells

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Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Creutzfeldt–Jakob disease (CJD) are brain conditions affecting millions of people worldwide. These diseases are associated with the presence of amyloid-β (Aβ), alpha synuclein (α-Syn) and prion protein (PrP) depositions in the brain, respectively, which lead to synaptic disconnection and subsequent progressive neuronal death. Although considerable progress has been made in elucidating the pathogenesis of these diseases, the specific mechanisms of their origins remain largely unknown. A body of research suggests a potential association between host microbiota, neuroinflammation and dementia, either directly due to bacterial brain invasion because of barrier leakage and production of toxins and inflammation, or indirectly by modulating the immune response. In the present review, we focus on the emerging topics of neuroinflammation and the association between components of the human microbiota and the deposition of Aβ, α-Syn and PrP in the brain. Special focus is given to gut and oral bacteria and biofilms and to the potential mechanisms associating microbiome dysbiosis and toxin production with neurodegeneration. The roles of neuroinflammation, protein misfolding and cellular mediators in membrane damage and increased permeability are also discussed.

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Section: Protein Misfolding and Its Accumulation In Neurodegeneratmentioning

confidence: 99%

Section: Protein Misfolding and Its Accumulation In Neurodegeneratmentioning

confidence: 99%

Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration

González-Sanmiguel

Schuh

Muñoz-Montesino

et al. 2020

Cells

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“…The prion protein (PrP) is located intracellularly and is also an important membrane-bound protein at the cell surface. Therefore, PrP is involved in exocytotic and endocytic synaptic vesicle processing as well as in signaling pathways, but also in myelination and neurogenesis (Liebert et al, 2014; Legname, 2017; Watts et al, 2018).…”

Section: Iron and Protein Aggregationmentioning

confidence: 99%

The Contribution of Iron to Protein Aggregation Disorders in the Central Nervous System

et al. 2019

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The homeostasis of iron is of fundamental importance in the central nervous system (CNS) to ensure biological processes such as oxygen transport, mitochondrial respiration or myelin synthesis. Dyshomeostasis and accumulation of iron can be observed during aging and both are shared characteristics of several neurodegenerative diseases. Iron-mediated generation of reactive oxygen species (ROS) may lead to protein aggregation and cellular toxicity. The process of misfolding and aggregation of neuronal proteins such as α-synuclein, Tau, amyloid beta (Aβ), TDP-43 or SOD1 is a common hallmark of many neurodegenerative disorders and iron has been shown to facilitate protein aggregation. Thus, both, iron and aggregating proteins are proposed to amplify their detrimental effects in the disease state. In this review, we give an overview on effects of iron on aggregation of different proteins involved in neurodegeneration. Furthermore, we discuss the proposed mechanisms of iron-mediated toxicity and protein aggregation emphasizing the red-ox chemistry and protein-binding properties of iron. Finally, we address current therapeutic approaches harnessing iron chelation as a disease-modifying intervention in neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis.

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“…See table of abbreviations for explanation of abbreviations. (See Aguzzi et al, 2008;Castle and Gill, 2017;Didonna, 2013;Liebert et al, 2014;Linden, 2017;Miranzadeh Mahabadi and Taghibiglou, 2020;Puig et al, 2020;Sorgato et al, 2009;Steinert, 2015;Watts et al, 2018;Wulf et al, 2017). Modulates NF-κB (NF-κB implicated in adult neurogenesis and structural plasticity).…”

Section: Trem2mentioning

confidence: 99%

Alzheimer’s disease as a syndrome of overloaded amyloidic synaptic tagging in memory networks

Murphy¹

2021

Preprint

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Alzheimer’s Disease is defined as progressive memory loss coincident with accumulation of aggregated amyloid beta and phosphorylated tau. Identifying the relationship between these features has guided Alzheimer’s Disease research for decades, principally with the view that aggregated proteins drive a neurodegenerative process. Here I propose that amyloid beta and phospho-tau write-protect and tag neuroplastic changes as they form, protecting and insuring established neuroplasticity from corruption. In way of illustration, binding of oligomeric amyloid beta to the prion receptor is presented as an example possible mechanism. The write-protecting process is conjected to occur at least partially under the governance of isodendritic neuromodulators such as norepinephrine and acetylcholine. Coincident with aging, animals are exposed to accumulating amounts of memorable information. Compounded with recent increases in life expectancy and exposure to information-rich environments this causes aggregating proteins to reach unforeseen toxic levels as mnemonic circuits overload. As the brain cannot purposefully delete memories nor protect against overaccumulation of aggregating proteins, the result is catastrophic breakdown on cellular and network levels causing memory loss.

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Prion Protein Signaling in the Nervous System—A Review and Perspective

Cited by 10 publications

References 268 publications

Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration

Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration

The Contribution of Iron to Protein Aggregation Disorders in the Central Nervous System

Alzheimer’s disease as a syndrome of overloaded amyloidic synaptic tagging in memory networks

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