Axonal changes in experimental prion diseases recapitulate those following constriction of postganglionic branches of the superior cervical ganglion: a comparison 40 years later

Liberski, Paweł P.

doi:10.1080/19336896.2019.1595315

Cited by 9 publications

(10 citation statements)

References 60 publications

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“…Membrane PrP C acts as a receptor for Aβ oligomers; this feature helps explain its involvement in AD development [ 16 ]. Nonetheless, both AD and CJD have been described as having very similar dystrophic neurites containing mostly autophagic vacuoles and autophagosomes [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Protein Aggregates Colocalization and Neuronal Dystrophy in Comorbid Alzheimer’s and Creutzfeldt–Jakob Disease: A Micromorphological Pilot Study on 20 Brains

Jankovska

Olejár

Matěj

2021

IJMS

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Alzheimer’s disease (AD) and sporadic Creutzfeldt–Jakob disease (sCJD) are both characterized by extracellular pathologically conformed aggregates of amyloid proteins—amyloid β-protein (Aβ) and prion protein (PrPSc), respectively. To investigate the potential morphological colocalization of Aβ and PrPSc aggregates, we examined the hippocampal regions (archicortex and neocortex) of 20 subjects with confirmed comorbid AD and sCJD using neurohistopathological analyses, immunohistochemical methods, and confocal fluorescent microscopy. Our data showed that extracellular Aβ and PrPSc aggregates tended to be, in most cases, located separately, and “compound” plaques were relatively rare. We observed PrPSc plaque-like structures in the periphery of the non-compact parts of Aβ plaques, as well as in tau protein-positive dystrophic structures. The AD ABC score according to the NIA-Alzheimer’s association guidelines, and prion protein subtype with codon 129 methionine–valine (M/V) polymorphisms in sCJD, while representing key characteristics of these diseases, did not correlate with the morphology of the Aβ/PrPSc co-aggregates. However, our data showed that PrPSc aggregation could dominate during co-aggregation with non-compact Aβ in the periphery of Aβ plaques.

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Section: Introductionmentioning

confidence: 99%

Extracellular Protein Aggregates Colocalization and Neuronal Dystrophy in Comorbid Alzheimer’s and Creutzfeldt–Jakob Disease: A Micromorphological Pilot Study on 20 Brains

Jankovska

Olejár

Matěj

2021

IJMS

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“…The pathogenesis of dystrophic neurites, another constant neurodegenerative alteration in TSE, is also unclear. It has been suggested that autophagic vacuoles originate in the neuronal cell body, flow down with axonal transport along the neurites, and then, in the presence of an impairment of that transport, are accumulated forming dystrophic neurites (Liberski et al, 2011;Liberski, 2019), a reasoning which resembles that described in AD (Nixon, 2007;Boland et al, 2008).…”

Section: Autophagy In Prion Neuropathologymentioning

confidence: 90%

An Update on Autophagy in Prion Diseases

López-Pérez

Badiola

Bolea

et al. 2020

Front. Bioeng. Biotechnol.

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Autophagy is a dynamic intracellular mechanism involved in protein and organelle turnover through lysosomal degradation. When properly regulated, autophagy supports normal cellular and developmental processes, whereas defects in autophagic degradation have been associated with several pathologies, including prion diseases. Prion diseases, or transmissible spongiform encephalopathies (TSE), are a group of fatal neurodegenerative disorders characterized by the accumulation of the pathological misfolded isoform (PrP Sc ) of the physiological cellular prion protein (PrP c ) in the central nervous system. Autophagic vacuoles have been described in experimental models of TSE and in the natural disease in humans. The precise connection of this process with prion-related neuropathology, or even whether autophagy is completely beneficial or pathogenic during neurodegeneration, is poorly understood. Thus, the biological role of autophagy in these diseases is still open to debate. During the last years, researchers have used a wide range of morphological, genetic and biochemical methods to monitor and manipulate the autophagic pathway and thus determine the specific role of this process in TSE. It has been suggested that PrP c could play a crucial role in modulating the autophagic pathway in neuronal cells, and the presence of abnormal autophagic activity has been frequently observed in several models of TSE both in vitro and in vivo , as well as in human prion diseases. Altogether, these findings suggest that autophagy is implicated in prion neuropathology and points to an impairment or failure of the process, potentially contributing to the pathogenesis of the disease. Additionally, autophagy is now emerging as a host defense response in controlling prion infection that plays a protective role by facilitating the clearance of aggregation-prone proteins accumulated within neurons. Since autophagy is one of the pathways of PrP Sc degradation, and drug-induced stimulation of autophagic flux (the dynamic process of autophagic degradation activity) produces anti-prion effects, new treatments based on its activation have been tested to develop therapeutic strategies for prion diseases. In this review, we summarize previous and recent findings concerning the role of autophagy in TSE.

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“…The spongiosis (micro- and macrovacuolization) observed in this pathology, a differential characteristic of the group of transmissible spongiform diseases, has not been well elaborated thus far, although it is of great importance in diagnosis [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. In studies at the level of optical and electron microscopy, a large number of vacuoles with a size of 0.3 to 20 microns have been evidenced, outside the neurons in the neuropil.…”

Section: Considerations For Studies On Cerebellar Neuropathological Alterations In Classical Scrapiementioning

confidence: 99%

“…Similarly, whether the extraneuronal vacuolization in the neuropil is related to translucent vesicles observed in the soma and neuron dendrites has not been clarified. The neuronal autophagic vesicles/vacuoles could converge and then expand, and eventually, a vast area of the cytoplasm was transformed into a merging mass of autophagic vacuoles [ 75 ] ( Figure 7 ).…”

Section: Considerations For Studies On Cerebellar Neuropathological Alterations In Classical Scrapiementioning

confidence: 99%

Reflections on Cerebellar Neuropathology in Classical Scrapie

et al. 2021

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In this review, the most important neuropathological changes found in the cerebella of sheep affected by classical natural scrapie are discussed. This disease is the oldest known of a group of unconventional “infections” caused by toxic prions of different origins. Scrapie is currently considered a “transmissible spongiform encephalopathy” (due to its neuropathological characteristics and its transmission), which is the paradigm of prion pathologies as well as many encephalopathies (prion-like) that present aberrant deposits of insoluble protein with neurotoxic effects due to errors in their catabolization (“misfolding protein diseases”). The study of this disease is, therefore, of great relevance. Our work data from the authors’ previous publications as well as other research in the field. The four most important types of neuropathological changes are neuron abnormalities and loss, neurogliosis, tissue vacuolization (spongiosis) and pathological or abnormal prion protein (PrP) deposits/deposition. These findings were analyzed and compared to other neuropathologies. Various aspects related to the presentation and progression of the disease, the involution of different neuronal types, the neuroglial responses and the appearance of abnormal PrP deposits are discussed. The most important points of controversy in scrapie neuropathology are presented.

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Axonal changes in experimental prion diseases recapitulate those following constriction of postganglionic branches of the superior cervical ganglion: a comparison 40 years later

Cited by 9 publications

References 60 publications

Extracellular Protein Aggregates Colocalization and Neuronal Dystrophy in Comorbid Alzheimer’s and Creutzfeldt–Jakob Disease: A Micromorphological Pilot Study on 20 Brains

Extracellular Protein Aggregates Colocalization and Neuronal Dystrophy in Comorbid Alzheimer’s and Creutzfeldt–Jakob Disease: A Micromorphological Pilot Study on 20 Brains

An Update on Autophagy in Prion Diseases

Reflections on Cerebellar Neuropathology in Classical Scrapie

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