-
Seminars in Neurology Aug 2019Prion diseases are a phenotypically diverse set of disorders characterized by protease-resistant abnormally shaped proteins known as prions. There are three main groups... (Review)
Review
Prion diseases are a phenotypically diverse set of disorders characterized by protease-resistant abnormally shaped proteins known as prions. There are three main groups of prion diseases, termed sporadic (Creutzfeldt-Jakob disease [CJD], sporadic fatal insomnia, and variably protease-sensitive prionopathy), genetic (genetic CJD, fatal familial insomnia, and Gerstmann-Straussler-Scheinker syndrome), and acquired (kuru, variant CJD, and iatrogenic CJD). This article will review the pathophysiology, genetics, clinical presentations, and diagnostic challenges in patients with prion disease. Case discussions, images, and tables will be used to highlight important characteristics of prion disease and prion mimics.
Topics: Aged; Animals; Creutzfeldt-Jakob Syndrome; Diagnosis, Differential; Humans; Male; Middle Aged; Prion Diseases; Wernicke Encephalopathy
PubMed: 31533183
DOI: 10.1055/s-0039-1687841 -
Nature Reviews. Neurology Jun 2022Rapidly progressive dementias (RPDs) are a group of heterogeneous disorders that include immune-mediated, infectious and metabolic encephalopathies, as well as prion... (Review)
Review
Rapidly progressive dementias (RPDs) are a group of heterogeneous disorders that include immune-mediated, infectious and metabolic encephalopathies, as well as prion diseases and atypically rapid presentations of more common neurodegenerative diseases. Some of these conditions are treatable, and some must be diagnosed promptly because of their potential infectivity. Prion disease is considered to be the prototypical RPD, but over the past two decades, epidemiological reports and the identification of various encephalitis-mediating antibodies have led to a growing recognition of other encephalopathies as potential causes of rapid cognitive decline. Knowledge of RPD aetiologies, syndromes and diagnostic work-up protocols will help clinicians to establish an early, accurate diagnosis, thereby reducing morbidity and mortality, especially in immune-mediated and other potentially reversible dementias. In this Review, we define the syndrome of RPD and shed light on its different aetiologies and on secondary factors that might contribute to rapid cognitive decline. We describe an extended diagnostic procedure in the context of important differential diagnoses, discuss the utility of biomarkers and summarize potential treatment options. In addition, we discuss treatment options such as high-dose steroid therapy in the context of therapy and diagnosis in clinically ambiguous cases.
Topics: Brain Diseases; Dementia; Diagnosis, Differential; Disease Progression; Humans; Neurodegenerative Diseases; Prion Diseases
PubMed: 35508635
DOI: 10.1038/s41582-022-00659-0 -
Nature Reviews. Disease Primers Feb 2024Prion diseases share common clinical and pathological characteristics such as spongiform neuronal degeneration and deposition of an abnormal form of a host-derived... (Review)
Review
Prion diseases share common clinical and pathological characteristics such as spongiform neuronal degeneration and deposition of an abnormal form of a host-derived protein, termed prion protein. The characteristic features of prion diseases are long incubation times, short clinical courses, extreme resistance of the transmissible agent to degradation and lack of nucleic acid involvement. Sporadic and genetic forms of prion diseases occur worldwide, of which genetic forms are associated with mutations in PRNP. Human to human transmission of these diseases has occurred due to iatrogenic exposure, and zoonotic forms of prion diseases are linked to bovine disease. Significant progress has been made in the diagnosis of these disorders. Clinical tools for diagnosis comprise brain imaging and cerebrospinal fluid tests. Aggregation assays for detection of the abnormally folded prion protein have a clear potential to diagnose the disease in peripherally accessible biofluids. After decades of therapeutic nihilism, new treatment strategies and clinical trials are on the horizon. Although prion diseases are relatively rare disorders, understanding their pathogenesis and mechanisms of prion protein misfolding has significantly enhanced the field in research of neurodegenerative diseases.
Topics: Animals; Cattle; Humans; Creutzfeldt-Jakob Syndrome; Prion Proteins; Prion Diseases; Brain
PubMed: 38424082
DOI: 10.1038/s41572-024-00497-y -
Medicina Clinica Jun 2023Prion diseases are a group of neurodegenerative diseases. The disease-causing agent is a protein (PrP), that is normally produced in the nervous system, aggregated in an... (Review)
Review
Prion diseases are a group of neurodegenerative diseases. The disease-causing agent is a protein (PrP), that is normally produced in the nervous system, aggregated in an abnormal form. The abnormal protein, known as prion (PrP), is capable of self-propagation promoting the misfolding of the normal protein (PrP). These conditions can be acquired sporadically, genetically, or infectiously either by eating meat contaminated with prions or from iatrogenic exposure. The diagnosis of these diseases is often challenging. The use of highly sensitive and specific diagnostic tools, such as MRI and RT-QuIC, may aid in the diagnosis. Neuropathological examination of brain tissue ensures a definite diagnosis. At present, no treatment significantly improves the course of prion diseases; however, an early diagnosis is of paramount importance for patient care decision planning, infection control purposes, and genetic counseling.
Topics: Humans; Creutzfeldt-Jakob Syndrome; Prion Diseases; Prions; Brain
PubMed: 37088611
DOI: 10.1016/j.medcli.2023.03.001 -
Advances in Experimental Medicine and... 2020Prion disease, also known as transmissible spongiform encephalopathy (TES), is a fatal neurodegenerative disease caused by prion protein. The most important pathogenesis... (Review)
Review
Prion disease, also known as transmissible spongiform encephalopathy (TES), is a fatal neurodegenerative disease caused by prion protein. The most important pathogenesis is related to changes in the conformation of cellular prion proteins (PrP). The histopathological features of prion disease are spongiform degeneration, neuronal deficiency, glial activation and the deposition of amyloid-like PrP. Cellular prion protein, ubiquitously expressed in the brain and other tissues, is transformed into the PrP (PrP) isoform in the prion disease. In this chapter, we summarize the research progresses of prion disease, the structural organization and normal function of PrP in the central nervous system. Moreover, the formation and transmissibility of prion aggregations (PrP) were also included. But we mainly focused on the function of PrP in autophagy. Several autophagic-related markers, such as p62 and LC3, are significantly upregulated in models of prion disease. Recent advances in the autophagic invention in prion disease and several pharmaceutical targets of autophagy were reviewed in this chapter. It is necessary to understand how the prion protein spread, transport and recycle, and what is the relationship between the clearance and autophagy.
Topics: Autophagy; Humans; Prion Diseases; Prion Proteins
PubMed: 32671739
DOI: 10.1007/978-981-15-4272-5_4 -
Science (New York, N.Y.) Jan 2024My first encounter with prion diseases dates to 1986. As a clinical resident in neuropathology, I was tasked with performing autopsies of patients who died of mysterious...
My first encounter with prion diseases dates to 1986. As a clinical resident in neuropathology, I was tasked with performing autopsies of patients who died of mysterious brain diseases. In his early 60s, my patient had developed a form of dementia that progressed at a terrifyingly rapid pace and eventually led to his death. I sampled the patient's brain and processed it for histological examination. The microscope revealed an eerie landscape of destruction. All that was left in the patient's cortex were astrocytes and microglia, and the few remaining neurons showed extensive vacuolation of their bodies and processes. Such blazing destruction of the brain was indicative of just one diagnosis: Creutzfeldt-Jakob disease, a spongiform encephalopathy caused by enigmatic infectious agents called prions.
Topics: Humans; Cerebral Cortex; Creutzfeldt-Jakob Syndrome; Prion Diseases; Prions
PubMed: 38236962
DOI: 10.1126/science.adn9424 -
Cell and Tissue Research Apr 2023Prion diseases are devastating neurodegenerative diseases caused by the structural conversion of the normally benign prion protein (PrP) to an infectious,... (Review)
Review
Prion diseases are devastating neurodegenerative diseases caused by the structural conversion of the normally benign prion protein (PrP) to an infectious, disease-associated, conformer, PrP. After decades of intense research, much is known about the self-templated prion conversion process, a phenomenon which is now understood to be operative in other more common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In this review, we provide the current state of knowledge concerning a relatively poorly understood aspect of prion diseases: mechanisms of neurotoxicity. We provide an overview of proposed functions of PrP and its interactions with other extracellular proteins in the central nervous system, in vivo and in vitro models used to delineate signaling events downstream of prion propagation, the application of omics technologies, and the emerging appreciation of the role played by non-neuronal cell types in pathogenesis.
Topics: Humans; Prions; Prion Diseases; Prion Proteins; Neurodegenerative Diseases; Alzheimer Disease
PubMed: 36070155
DOI: 10.1007/s00441-022-03683-0 -
International Journal of Molecular... Feb 2021Neuroinflammation, typically manifest as microglial activation and astrogliosis accompanied by transcriptomic alterations, represents a common hallmark of various... (Review)
Review
Neuroinflammation, typically manifest as microglial activation and astrogliosis accompanied by transcriptomic alterations, represents a common hallmark of various neurodegenerative conditions including prion diseases. Microglia play an overall neuroprotective role in prion disease, whereas reactive astrocytes with aberrant phenotypes propagate prions and contribute to prion-induced neurodegeneration. The existence of heterogeneous subpopulations and dual functions of microglia and astrocytes in prion disease make them potential targets for therapeutic intervention. A variety of neuroinflammation-related molecules are involved in prion pathogenesis. Therapeutics targeting neuroinflammation represents a novel approach to combat prion disease. Deciphering neuroinflammation in prion disease will deepen our understanding of pathogenesis of other neurodegenerative disorders.
Topics: Animals; Brain; Chemokines; Cytokines; Gliosis; Humans; Inflammation; Microglia; Phagocytosis; Prion Diseases; Toll-Like Receptors
PubMed: 33672129
DOI: 10.3390/ijms22042196 -
International Journal of Molecular... Jul 2021The principal pathogenic event in Parkinson's disease is characterized by the conformational change of α-synuclein, which form pathological aggregates of misfolded... (Review)
Review
The principal pathogenic event in Parkinson's disease is characterized by the conformational change of α-synuclein, which form pathological aggregates of misfolded proteins, and then accumulate in intraneuronal inclusions causing dopaminergic neuronal loss in specific brain regions. Over the last few years, a revolutionary theory has correlated Parkinson's disease and other neurological disorders with a shared mechanism, which determines α-synuclein aggregates and progresses in the host in a prion-like manner. In this review, the main characteristics shared between α-synuclein and prion protein are compared and the cofactors that influence the remodeling of native protein structures and pathogenetic mechanisms underlying neurodegeneration are discussed.
Topics: Animals; Dopaminergic Neurons; Humans; Parkinson Disease; Prion Diseases; Protein Aggregates; alpha-Synuclein; tau Proteins
PubMed: 34360787
DOI: 10.3390/ijms22158022 -
Neuroscience Letters Jan 2021Multiple system atrophy (MSA) is an atypical parkinsonism that rapidly affects motor ability and autonomic function, leaving patients wheelchair-bound and dependent for... (Review)
Review
Multiple system atrophy (MSA) is an atypical parkinsonism that rapidly affects motor ability and autonomic function, leaving patients wheelchair-bound and dependent for daily activities in 3-5 years. Differential diagnosis is challenging as cases may resemble Parkinson's disease or other ataxic syndromes depending on the clinical variant (MSA-P or MSA-C), especially in early stages. There are limited symptomatic treatments and no disease-modifying therapies. Pathologically, alpha-synuclein aggregates are found in glial cytoplasmic inclusions, among other proteins, as well as in neurons. The molecular pathogenesis of the disease, however, is widely unknown. Transcriptomic studies in MSA have tried to unravel the pathological mechanisms involved in the disease. Several biological and molecular processes have been described in the literature that associate disease pathogenesis with inflammation, mitochondrial, and autophagy related dysfunctions, as well as prion disease and Alzheimer disease associated pathways. These reports have also registered several differential diagnostic biomarker candidates. However, cross-validation between studies, in general, is poor, making clinical applicability and data reliability very challenging. This review will go over the main transcriptomic studies done in MSA, reporting on the most significant transcriptive and post-transcriptive changes described, and focusing on the main consensual findings.
Topics: Epigenomics; Humans; MicroRNAs; Multiple System Atrophy; Prion Diseases; Transcriptome
PubMed: 33352281
DOI: 10.1016/j.neulet.2020.135586