Propagation and Dissemination Strategies of Transmissible Spongiform Encephalopathy Agents in Mammalian Cells

Heumüller, Stefanie-Elisabeth; Hornberger, Annika; Hebestreit, Alina; Hossinger, André; Vorberg, Ina

doi:10.3390/ijms23062909

Cited by 7 publications

(7 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PrP Sc propagates through four main mechanisms: direct cell-to-cell contact, tunneling nanotubes, GPI painting (spontaneous incorporation of GPI-protein into the cell surface membrane), and extracellular vesicles ( Heumüller et al, 2022 ). Alterations of the lipid membrane profile may interfere with many of these processes: (i) Changes in GPI anchor or even detachment of PrP from the cell membrane will directly interfere with cell-to-cell propagation and GPI painting.…”

Section: Discussionmentioning

confidence: 99%

What is the role of lipids in prion conversion and disease?

Conceição

Lemos

Barros

et al. 2023

Front. Mol. Neurosci.

View full text Add to dashboard Cite

The molecular cause of transmissible spongiform encephalopathies (TSEs) involves the conversion of the cellular prion protein (PrPC) into its pathogenic form, called prion scrapie (PrPSc), which is prone to the formation of amorphous and amyloid aggregates found in TSE patients. Although the mechanisms of conversion of PrPC into PrPSc are not entirely understood, two key points are currently accepted: (i) PrPSc acts as a seed for the recruitment of native PrPC, inducing the latter’s conversion to PrPSc; and (ii) other biomolecules, such as DNA, RNA, or lipids, can act as cofactors, mediating the conversion from PrPC to PrPSc. Interestingly, PrPC is anchored by a glycosylphosphatidylinositol molecule in the outer cell membrane. Therefore, interactions with lipid membranes or alterations in the membranes themselves have been widely investigated as possible factors for conversion. Alone or in combination with RNA molecules, lipids can induce the formation of PrP in vitro-produced aggregates capable of infecting animal models. Here, we discuss the role of lipids in prion conversion and infectivity, highlighting the structural and cytotoxic aspects of lipid-prion interactions. Strikingly, disorders like Alzheimer’s and Parkinson’s disease also seem to be caused by changes in protein structure and share pathogenic mechanisms with TSEs. Thus, we posit that comprehending the process of PrP conversion is relevant to understanding critical events involved in a variety of neurodegenerative disorders and will contribute to developing future therapeutic strategies for these devastating conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

What is the role of lipids in prion conversion and disease?

Conceição

Lemos

Barros

et al. 2023

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Using specific exosome markers, MS and morphological analysis, both PrP c and PrP sc have been found to be released via endosome derived exosomes ( Fevrier et al, 2004 ). However, prion association has also been found associated with microvesicles ( Caughey et al, 2009 ; Heumuller et al, 2022 ; Kovac and Curin Serbec, 2022 ). Studies carried out by Leblanc et al (2006) have found that cells infected with retrovirus strongly enhance the release of PrP C and PrP Sc proteins via exosomes.…”

Section: Role Of Extracellular Vesicles In Dissemination Of Pathogeni...mentioning

confidence: 99%

Extracellular vesicles: A new paradigm in understanding, diagnosing and treating neurodegenerative disease

Dar

Badierah

Nathan

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

Neurodegenerative disorders (NDs) are becoming one of the leading causes of disability and death across the globe due to lack of timely preventions and treatments. Concurrently, intensive research efforts are being carried out to understand the etiology of these age-dependent disorders. Extracellular vesicles (EVs)—biological nanoparticles released by cells—are gaining tremendous attention in understanding their role in pathogenesis and progression of NDs. EVs have been found to transmit pathogenic proteins of NDs between neurons. Moreover, the ability of EVs to exquisitely surmount natural biological barriers, including blood-brain barrier and in vivo safety has generated interest in exploring them as potential biomarkers and function as natural delivery vehicles of drugs to the central nervous system. However, limited knowledge of EV biogenesis, their heterogeneity and lack of adequate isolation and analysis tools have hampered their therapeutic potential. In this review, we cover the recent advances in understanding the role of EVs in neurodegeneration and address their role as biomarkers and delivery vehicles to the brain.

show abstract

“…The infectious character of prion diseases is reflected at the cellular level by transfer of prion infectivity from cell to cell, inside and outside of the CNS, which results in the infection of naïve cells. Since cell culture models exist that recapitulate acute and persistent prion infection, the cell biology of intracellular generation of prions, interaction with cellular pathways and clearance mechanisms, and infection of new cells are rather well studied and subject of many review articles (Heiseke et al 2010;Priola 2017;Krance et al 2020;Heumüller et al 2022).…”

Section: Introductionmentioning

confidence: 99%

Vaccines for prion diseases: a realistic goal?

Napper

Schätzl

2023

Cell Tissue Res

View full text Add to dashboard Cite

Prion diseases are fatal infectious neurodegenerative disorders and prototypic conformational diseases, caused by the conformational conversion of the normal cellular prion protein (PrPC) into the pathological PrPSc isoform. Examples are scrapie in sheep and goat, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and Creutzfeldt–Jacob disease (CJD) in humans. There are no therapies available, and animal prion diseases like BSE and CWD can negatively affect the economy, ecology, animal health, and possibly human health. BSE is a confirmed threat to human health, and mounting evidence supports the zoonotic potential of CWD. CWD is continuously expanding in North America in numbers and distribution and was recently identified in Scandinavian countries. CWD is the only prion disease occurring both in wild and farmed animals, which, together with extensive shedding of infectivity into the environment, impedes containment strategies. There is currently a strong push to develop vaccines against CWD, including ones that can be used in wildlife. The immune system does not develop a bona fide immune response against prion infection, as PrPC and PrPSc share an identical protein primary structure, and prions seem not to represent a trigger for immune responses. This asks for alternative vaccine strategies, which focus on PrPC-directed self-antibodies or exposure of disease-specific structures and epitopes. Several groups have established a proof-of-concept that such vaccine candidates can induce some levels of protective immunity in cervid and rodent models without inducing unwanted side effects. This review will highlight the most recent developments and discuss progress and challenges remaining.

show abstract

Propagation and Dissemination Strategies of Transmissible Spongiform Encephalopathy Agents in Mammalian Cells

Cited by 7 publications

References 125 publications

What is the role of lipids in prion conversion and disease?

What is the role of lipids in prion conversion and disease?

Extracellular vesicles: A new paradigm in understanding, diagnosing and treating neurodegenerative disease

Vaccines for prion diseases: a realistic goal?

Contact Info

Product

Resources

About